Achievement Tips

Basic Achievement Tips

For achievements gained by getting a completion mark with a certain character, consult the relevant character and completion mark requirement for strategy tips.

For achievements gained by completing a challenge refer to the challenge's specific page.

Most other achievements involve doing a basic task repeatedly or having a lucky combination of items, and will be gained with natural play.

Super Meat Boy & Super Bandage Girl

See Unlocking Super Meat Boy & Super Bandage Girl.

Lachryphagy

Lachryphagy is unlocked by obtaining 10 Tears Up Items/Pills in one run. In normal gameplay this can be extremely rare, and is most often earned accidentally by obtaining this many items by chance. The following are some strategies for obtaining the achievement:

Each item collected counts towards the Achievement. Dropping a tears up an item will not count against the total. Progress towards the achievement is only tied to items and pills, and is not directly tied to the actual tears stat. As such, reaching the tear cap or collecting Tears Down pills or items will not count against the achievement.
Lazarus starts with a pill, so restarting repeatedly until they have a Tears Up pill ensures that the pill type will be available during the run. From there, prioritizing Mom's Bottle of Pills, Placebo and PHD will allow them to generate more of these pills. This can be much easier to do in Greed mode, as you can often reroll the shop items until you find these, as well as repeatedly buy pills until another Tears Up one appears.
Tainted Cain can craft items that count towards the achievement.
Obtaining a large number of items, then repeatedly rerolling them such as by using D4 can allow Isaac to get more Tears Up items. Losing a Tears Up item this way will not count against the achievement.
A Golden Pill can be used if Tears Up is not a part of the current run's Pill pool, where when used repeatedly can grant many Tears Up bonuses, but this is very luck-based.
Many Tears Up items come from the Item Room and Boss Room pools. The Pact and Dark Prince's Crown can be found in the Devil Deal and Curse Room Pools, whilst Act of Contrition can only be found in the Angel Pool, and Odd Mushroom is the only item in the Secret Room Pool that counts towards the achievement. This means collecting as many boss room drops as possible is preferred, but in general going after all item pools is a good idea. The odds of getting tears up items from boss drops can be increased by using IV - The Emperor? successfully, and Pandora's Box on specific floors.

Only items internally tagged tearsup, as well as any Tears Up pills, will count towards unlocking Lachryphagy. This includes the following items.

Name	ID	Quote	Description	Quality
Anti-Gravity	5.100.222	Anti-gravity tears + tears up	Tears float in position until firing ceases, after which they will fly off in the direction they were shot in. -2 Tear Delay. +1 Fire Rate.	2
Blue Cap	5.100.342	HP + tears up + shot speed down	Gives one full Red Heart container, +0.7 tears, and -0.16 shot speed. Heals 1 additional Red Heart.	3
Capricorn	5.100.307	All stats up	Adds 1 Red Heart Container, gives +0.5 Damage, +0.1 Speed, +1.5 Range, and -1.0 Tear Delay, and gives 1 Bomb, Penny, and Key. Adds 1 Red Heart Container, gives +0.5 Damage, +0.1 Speed, +0.75 Range, and +0.5 Fire Rate, and gives 1 Bomb, Penny, and Key.	3
Cricket's Body	5.100.224	Bursting shots + tears up	When tears hit an object or deplete their range, they spawn 4 smaller tears, whose range and damage scale with Isaac's. Grants -1 tear delay and reduces range. Grants +0.5 fire rate and reduces range.	3
Guillotine	5.100.206	DMG + tears up. An out-of-body experience!	Isaac's head is removed from his body and floats around him as an orbital. Gives +1 damage and grants -1 tear delay. Gives +1 damage and grants +0.5 fire rate.	2
Mom's Perfume	5.100.228	Fear shot + tears up	Adds a chance to shoot fear tears. Decreases tear delay by 1. +0.5 fire rate.	2
Number One	5.100.6	Tears up + range down	Grants +1.5 tears, but severely reduces range.	2
Odd Mushroom	5.100.120	Tears + speed up, DMG down	+1.7 tears, +0.3 speed, slightly reduces damage.	2
Pisces	5.100.309	Tears up + knock-back shots	-1 Tear Delay, adds knock-back shots and increases tear size. +0.5 Fire Rate, adds knock-back shots and increases tear size.	2
Screw	5.100.255	Tears + shot speed up	+0.5 tears, +0.2 shot speed.	3
Soy Milk	5.100.330	DMG down + tears way up	Tears are smaller and do much less damage, but fire in very rapid succession.	2
Squeezy	5.100.196	Tears up	Increases tears by 0.4, spawns 2 Soul Hearts.	3
The Halo	5.100.101	All stats up	Grants one full Red Heart container, +0.3 damage, +0.2 tears, +0.25 range, +0.3 speed, and +0.5 tear falling speed. Grants one full Red Heart container, +0.3 damage, +0.2 tears, +1.5 range, and +0.3 speed. Heals 1 additional Red Heart.	2
The Pact	5.100.80	DMG + tears up	Grants two Soul Hearts, +0.5 damage, and +0.7 tears. Grants two Black Hearts, +0.5 damage, and +0.7 tears.	3
The Sad Onion	5.100.1	Tears up	Increases tears by 0.7.	3
The Small Rock	5.100.90	DMG up + speed down	+1 damage, +0.2 tears, -0.2 speed.	3
Tooth Picks	5.100.183	Tears + shot speed up	+0.7 tears, +0.16 shot speed.	3
Torn Photo	5.100.341	Tears + shot speed up	+0.7 tears, +0.16 shot speed.	3
Wire Coat Hanger	5.100.32	Tears up	Increases tears by 0.7.	3
Binky	5.100.438	Tears up	Grants one Soul Heart, +0.75 tears and decreases Isaac's size.	3
Eden's Blessing	5.100.381	Tears up + your future shines brighter	+0.7 tears up. Grants a random item at the start of the next run.	3
Marked	5.100.394	Directed tears	Isaac will automatically fire tears directed at a red target on the ground. The target can be moved with tear controls. +0.7 tears, increases range.	1
Mr. Dolly	5.100.370	Range + tears up	+0.7 tears, +5.25 range, +0.5 tear falling speed, Spawns a combination of 3 Red Hearts, Soul Hearts or Black Hearts on the floor when picked up. +0.7 tears, +2.5 range, spawns 3 random types of Hearts on the floor when picked up.	3
Purity	5.100.407	Aura stat boost	Boosts one of Isaac's stats depending on the color of the aura around him. The aura disappears upon taking damage and reappears with a random color upon entering a new room. Red boosts damage, blue boosts tears, yellow boosts speed, and orange boosts range.	3
Analog Stick	5.100.465	360 tears!	+0.35 tears up. Allows Isaac to fire tears diagonally.	2
Apple!	5.100.443	Trick or treat?	+0.3 tears. Adds a chance to fire a razor blade that deals 4x Isaac's damage.	3
Dark Prince's Crown	5.100.442	Loss is power	When at exactly one Red Heart, increases tears, range, tear falling speed, and shot speed. When at exactly one Red Heart, increases fire rate, range, and shot speed.	1
A Bar of Soap	5.100.564	Tears + shot speed up	Gives Isaac +0.5 Tears and +0.2 Shot Speed.	3
Act of Contrition	5.100.601	Tears up, you feel forgiven	Increases tears and grants an Eternal Heart. Allows Angel Rooms to appear even if a Devil Deal has been taken before. Reduces the Devil/Angel room chance penalty for taking Red heart damage.	3
Almond Milk	5.100.561	DMG down + tears up + you feel nutty	Quadruples fire rate, with x0.3 damage multiplier. Each tear is a given random effect that alters its movement.	1
Consolation Prize	5.100.644	+1 to lowest stat	Increases Isaac's lowest stat and drops either 3 Coins, 1 Bomb, or 1 Key depending on what Isaac has the least of.	1
Eye Drops	5.100.600	Tears up	Increases the fire rate in Isaac's left eye, causing his eyes to fire at different rates.	3
Paschal Candle	5.100.567	Keep the flame burning	Gives Isaac a familiar that grants +0.4 Fire Rate for each consecutive room he's cleared without taking damage. The bonus stacks up to five times.	3
Pluto	5.100.598	Size down	+0.7 tears. Significantly shrinks Isaac, allowing him to squeeze between objects and makes some enemy shots pass over him.	3

Note that no active items count towards unlocking Lachryphagy.

The following items do not count towards unlocking Lachryphagy, despite increasing tears:

It is unknown if the trinket effects from Cancer or Wiggle Worm count towards the achievement or not.

Obscure Challenge Achievements

These achievements involve performing a specific task without prompting.

5 Nights at Mom's: Get a 5-win streak, using a different character for each win. 3-win streak, using a different character for each win.

Earning the second will ensure earning the first. Win Streaks count all types of ending including Greed mode, but the achievements will not trigger if the final win is Greed or Greedier mode. Intentionally beating Isaac (Boss) or Satan without the item to continue to chapter 6 counts as a win. Beating Mom's Heart (before unlocking It Lives) counts as a win. If enough characters have been unlocked, consider going for this achievement early on in a new save file. Resetting the run in any way will break the streak.

ZIP!: Defeat The Lamb in under 20 minutes.

The Dark Room can be quickly reached by hitting the Sacrifice Room spikes 12 times. Consider using Azazel for quickly clearing floors, Isaac with The D6 for maximizing chances of a winning item combination, or Magdalene for a large source of hearts to sacrifice.

It's the Key: Defeat The Lamb without taking hearts, coins, and bombs through an entire run.

This challenge is only concerned with picking up hearts, coins, and bombs off the ground. Items that directly increase your inventory such as 2 of Clubs will not break the run. Be very careful around items that spawn pickups onto the ground, and chests. An alternative source of explosions such as Bob's Rotten Head is valuable in a run where bombs are rare. Magdalene is the only character with a certain source of healing, and is recommended for attempting this run with minimal difficulty. This can also be played as a slightly more challenging normal run for The Lost for more experienced players. Tainted Cain is also a good choice, since his Bag of Crafting can be used to grab pickups without any downside. The challenge will only be lost if Cain himself grabs any hearts, coins, or bombs.

No Damage Achievements

No Damage achievements are some of the most difficult achievements in the game. There are five of these achievements included in Rebirth, with 4 new achievements with similar objectives added in Afterbirth † with Booster Pack 5. The achievements are as follows:

Objective	Achievements
Beat chapter 1 without taking damage.	Basement Boy Sprinkler
Beat chapter 2 without taking damage.	Spelunker Boy Telekinesis
Beat chapter 3 without taking damage.	Dark Boy Leprosy
Beat chapter 4 without taking damage.	Mama's Boy Pop!
Beat chapter 6 without taking damage.	Dead Boy

Note that there is no achievement for completing Sheol or the Cathedral this way.

What Doesn't Count as Taking Damage

Using any item that causes self damage (Blood Rights, Razor Blade, IV Bag or Sharp Plug)
Using health on a Blood Donation Machine or a Devil Beggar
Taking a deal with the Devil
Using a Health Down pill
Resetting damage with Error: The given collectible ("Glowing Hour Glass") does not exist.
Getting hit while having Holy Mantle active

What Counts as Taking Damage

Getting hit by:
- Bombs
- Enemies
- Enemy projectiles
- Spikes (except Sacrifice Room spikes)
- Other hazards
Stepping on Curse Room spikes
Using a Bad Trip pill

Items

The lists below assume the player has not taken any damage that causes the player to miss out on the achievements.

Good Items

Holy Mantle blocks one hit per room, and it doesn't count as damage for these achievements.
Error: The given collectible ("Glowing Hour Glass") does not exist.
Infamy
Gnawed Leaf
Any item that increases damage (even temporarily), such as The Book of Belial
Any item that provides flight
- Callus, to a lesser extent
Any item that provides spectral tears
Items that provide invincibility, such as the Book of Shadows or Unicorn Stump
The Bible kills Mom and Mom's Heart/It Lives instantly when used during those boss fights.
Pyromaniac grants immunity to all explosions.
Orbitals that can block enemy shots
Flush!
IV - The Emperor can save you trying to find your way to the boss room.
The Ludovico Technique
Abaddon
Whore of Babylon
The The D6 can reroll a useless item into a better item (like the ones mentioned above).

Neutral Items

Iron Bar's concussive tears cause enemies to move around unpredictably.
Thunder Thighs and Leo can be used as an alternative to bombs to break Tinted Rocks (though they mostly drop Soul Hearts) and possibly find a Crawl Space or Black Market but should be used with great care, as stepping on a Bomb Rock or a bad Mushroom will damage the player and disqualify the achievement.
- Thunder Thighs is also a speed down and a useless health up.
Fire Mind's explosions can damage you if you are too close.
Dark Bum usually drops useless Soul Hearts, but occasionally spawns Blue Spiders or Spiders instead.
Mom's Toenail can hurt you.
Teleporting items.
- Teleporting into the I AM ERROR room can cause the player to miss out on a boss item, or even the achievement itself if it is the floor that they would have got it on.
The Wafer generally won't help, as the player would be trying not to take any damage in the first place. However, it can be used in conjunction with self-damaging items, even in Womb/Utero and beyond.

Bad Items

Any items that only give health are useless.
- Bucket of Lard gives 2 Red Heart containers and heals half a Red Heart but is also a speed down.
Strange Attractor can cause unpredictable enemy movement, especially with enemies like Dips and Boom Flies.
Explosive items such as Anarchist Cookbook should be used with extreme care.

Characters

Isaac

Isaac is very advisable once The D6 is unlocked; an active item which can be extremely useful to reroll bad items into better items that makes the runs easier.
If you have not unlocked The D6, Isaac is less advisable than ???, who has slightly better base stats as Isaac.

Magdalene

Magdalene is not a very good choice since she starts with 4 health and the Yum Heart. She also has a low base speed, which makes it hard to avoid enemies that run into you.
Upon completion of the Aprils fool challenge, Magdalene starts each run holding a Speed Up pill, allowing her speed to be set to 1.0 from the beginning of the run, allowing for easier dodging.
- She now starts off with a Full Health Pill instead, which forces her to keep her low base speed until a Speed Up Item or pill is found.

Judas

Judas is a very advisable character, since he starts with a higher damage multiplier than most characters, and The Book of Belial. Being able to deal more damage means less time dealing with enemies and bosses, and clearing rooms faster. His low health is not a drawback in this case, as long as the player is skilled enough to avoid damage.

Samson

Samson is less advisable than Isaac, as Bloody Lust only increases his damage whenever he takes damage. This leads to a dilemma; Samson must either avoid damage for a higher Devil Room or Angel Room chance, or take damage to take advantage of Bloody Lust.

Azazel

Azazel is extremely advisable, as he starts with flight and a short-ranged version of Brimstone. Azazel's flight allows Azazel to have increased mobility and hide behind obstacles, which helps counteract his lack of range with Brimstone on early floors. Azazel's short-ranged Brimstone deals significantly more damage than any other character; allowing Azazel to quickly get through early floors.

???

??? has slightly better stats than Isaac, making him an advisable character to play.
??? has some advantages over other characters when picking up certain items, since he cannot gain Red Heart containers. For example, Whore of Babylon is permanently active for ??? once picked up.

Lazarus

Lazarus is not advisable, as he has low range and starts with a random pill; this makes him slightly worse than non-The D6 Isaac.
If Lazarus dies, he resurrects as Lazarus Risen - starting with increased stats and the effect of Anemic, which negates his low range. However, Lazarus cannot get the current chapter's achievement if he takes damage to kill himself.
After beating the Backasswards challenge, Lazarus now begins with Anemic, making his stats roughly equal to Isaac's.

Eden

Eden is inadvisable due to their randomness and the fact that Mom's Heart/It Lives need to be killed several times to play as Eden for several runs; if Eden starts with a poor set of items, then the player will have to waste another Eden Token.

The Lost

The Lost has no health (although internally he has half a Soul Heart), which can be used to encourage the player to get these achievements, as he can't take damage without dying. He also has flight and can take any Devil deals for free. However, strategies such as using Blood Donation Machines won't work with him unless he has extra lives.
The Lost begins with Holy Mantle after donating 879 coins to the Greed Donation Machine, allowing him to take one hit on rooms without dying.

Lilith

Lilith is not recommended for these achievements, as she relies on Incubus to deal damage, and is Blindfolded, which can leave her open to damage if the player isn't careful.

Keeper

Keeper is not recommended for these achievements, as he is the slowest character in the game (tied with Magdalene), and has a tear delay of 28, the slowest fire rate besides Azazel. The combination of these two factors will have Keeper open to attack much of the time, which is made worse by his slow speed, making it harder to dodge.

Apollyon

Apollyon is recommended for these achievements, as he starts with average stats and Void, an item which absorbs other items. Void gives stat increases to Apollyon when passive items are absorbed, and uses the effects of any absorbed active items every time Void is used.

Strategies

If possible, maximize the number of times you get to use The D6.
Use bombs to escape rooms that you don't think you can handle.
Do not risk going over spikes, if you don't have flight.
A very easy way to achieve the Dark Boy/Mama's Boy is to obtain The Bible while holding IV - The Emperor. This can be used to skip the final floor of the Template:Stage/Template:Stage entirely.
- This is even more effective if the floor is affected by Curse of the Labyrinth.
- Picking up Starter Deck and holding the Rune of Ehwaz and IV - The Emperor in combination with the The Bible is also a viable strategy, although Rune of Ehwaz has a small chance of spawning a door to a Crawl Space instead.
Note that you gain the achievement after you defeat the second boss of a chapter, not after you go down to the next floor. This means, after getting the related achievement, you can go visit the rest of the floor (including the curse room if you have enough health) and obtain pickups that could help you get the later achievements.

Tainted Cain/Clicker Strategy For Collecting Completion Marks For Other Characters

Tainted Cain starts the game with Bag of Crafting which can be used to create almost any item in the game if you can find a recipe for it. Most importantly, it can be used to craft Clicker, which can then be used to become any Tainted character. By crafting Lazarus' Rags or Ankh and then dying, then Clicker can be used to become any non-Tainted character. If you carefully choose what items to craft to make a powerful combination and then use Clicker to become a different character, this can be a good way to get completion marks and their achievements for some of the most challenging characters in the game.

Strategy

Restarting the game until a Library is next to the starting room can produce more pickups for crafting on the first level.
Leaving pickups on the floor until all rooms are cleared (except in Depths II, unless you want to use The Fool to escape the room) can help take careful inventory of the available pickups to ensure you can craft as many useful items as possible.
Collecting a couple keys in every floor instead of crafting with them allows you to enter the Treasure Room and the Shop for more pickups.
Pills and cards can be purchased in the Shop and then dropped for crafting, but this doesn't work with other pickups like bombs and hearts.
Keep in mind that it may take a number of uses of Clicker to find the character you want to play as, and each use will remove your most recently collected item. So, after you have crafted all the items you want to keep, you may want to craft multiple passive items you don't care about to act as fuel.
Crafting in this way tends to be very slow, which means you probably won't reach the time limit for Hush or Boss Rush, but these can still be reached by crafting the alternate items to reach them (see item list below).
You can craft familiars multiple times to have multiple copies of that familiar.
Crafting Gnawed Leaf with other items to clear rooms easily not only makes overall success more likely, but the lack of damage also makes Angel Rooms more likely to spawn, which allows you fight the angels to eventually gain access to Mega Satan without having to take up an active item slot for the alternate entry methods.
If pursuing the Mother achievement, it may be best to avoid using clicking Clicker until after beating the boss of Mausoleum/Gehenna, because Siren can steal all of your familiars.
You can get completion marks for a number of different characters in the same run, so if none of the remaining completion marks for your current character are needed, you can always switch again.

Especially Useful Items

7 Seals: One of the more versatile familiars, in combination with Gnawed Leaf. Simple to craft if you can find an eternal heart.
Angry Fly: Easily crafted if you can find many hearts, such as in a Super Secret room with hearts, and is a useful aggressive familiar. Crafting three of them produces the Beelzebub transformation which makes you fly, making you immune to spikes and creep and allowing you to reach items behind rocks and behind holes.
The Battery: Can allow the Clicker to be used twice in quick succession, which can be helpful if want to change characters again and wouldn't have enough rooms to charge it.
Clicker: This is the most important item to this strategy, of course, as that is how you are going to change characters.
Dad's Key: Allows access to Mega Satan if you don't have the key familiars.
Dead Cat: If Dead Cat was the last item to be crafted, the Clicker will remove individual lives instead of the entire item, meaning much fewer items will need to be crafted for the Clicker to remove before getting to the desired character. However, since Dead Cat takes priority over items that revive you as a non-tainted character, this item is only worth crafting for completing tainted character completion marks. On the other hand, if Dead Cat is found naturally as a pedastal item it can be useful to revive as a non-tainted character and then take Dead Cat before using the Clicker.
Forget Me Now: Can be used to get the same completion marks with more than one character on the same run by restarting the floor.
Gnawed Leaf: In combination with familiars that attack without Isaac's input or items that cause damage on touch or using auras, can be powerful choice to getting even the most difficult completion marks.
Mama Mega!: Allows Boss Rush and Hush achievements to be reached without being under the time limit.
Mr. ME!: Allows access to Mega Satan if you don't have the key familiars.
R Key: Once you reach the end of the completion marks you can restart all of the levels to start over again with the same items. (Keep in mind that The Beast fight goes to cut scene immediately aftering winning, and Mega Satan sometimes does, in which case you will not have the opportunity to use the item)
Red Stew: If crafted after Rock Bottom, provides a substantial and permanent damage increase.
Rock Bottom: A useful item in many respects, but is especially useful when using the Clicker, because you keep the best stats of every character you become. This also allows you to keep improved stats from items even if they are removed.
Salvation: Can quickly destroy bosses that chase you, as well as the beams reaching far enemies when triggered.
Schoolbag: Allows more than one active item to be carried at once, which is important if using the alternate items to reach different completion marks.
Soy Milk: If collected after Rock Bottom allows a very high tear rate without lowering damage. Best to craft this after damage increasing items like Red Stew because of the low damage multiplier will result in higher damage in this order. If you remove this item with Clicker but still have Rock Bottom, you will keep the higher tear rate and also lose the low tear multiplier that would otherwise make it hard to increase damage.
Sharp Key: Allows access for the Mother completion mark without having to collect Knife Piece 1 and Knife Piece 2.
Sulfuric Acid: Allows you to enter all the secret rooms, destroy key blocks, find side entrances to Boss Challenge rooms and Curse Rooms. Collecting items in special rooms always provides one of the pickups necessary for crafting items from that room's item pool, so entrance to those rooms opens up a lot of recipe possibilities.

Character Notes

Jacob and Esau: Items are split randomly between Jacob and Esau, meaning several copies of Gnawed Leaf should be crafted to have a reasonably high chance of both characters getting the item when using the Gnawed Leaf strategy.
Tainted Jacob: Gnawed Leaf does not grant immunity from Dark Esau.
Tainted Lazarus: Becoming Dead Tainted Lazarus will grant all of the items to Dead Tainted Lazarus, so you will be without all of the crafted items every other room.
Tainted Lost: This strategy allows Tainted Lost to hold and use many useful items that he can otherwise never find.

Bug!	Becoming Tainted Isaac always crashes the game. You can continue from the last save/autosave to continue the run, but the order of transformations from Clicker is deterministic, meaning that this effectively stops you from continuing the run with the Clicker strategy.

Bug!	Becoming Tainted Forgotten does not spawn Tainted Soul, leaving you unable to walk and softlocking the game. Softlock can usually be avoided by crafting The Battery and always making sure that you have two full charges before using it, so you could use it again if you become Tainted Forgotten.

Bug!	Becoming Tainted Lazarus will make him spawn without Dead Tainted Lazarus, removing much of the challenge usually inherent in the character, and allowing Gnawed Leaf strategies to work. But saving and continuing will reset Tainted Lazarus to his usual state, so if you are trying to take advantage of this, be sure to play all the way through once you become Tainted LAzarus

Bug!	Becoming Tainted Jacob will make him spawn without Dark Esau for the current floor, which can remove the extra challenge usually inherent with Tainted Jacob for that initial floor.

Force Quit and File Manipulation

As a last resort, force quitting the game may help net achievements that remain elusive due to lack of skills and/or luck. A save game is generated whenever one exits a game to the menu or at the start of a new level. If one wishes to go back to the last save game, force quit the game (Force Quit on OS X, End Task on Windows, home button and then close the app on consoles) and then restart the game. The continue option will light up and then your last save game will be restored. Aside from helping with Achievements, this is useful if you want to reverse negative pill effects, exploit coin donation, find the quickest way through the level after doing a "test run", etc...

The method is also capable of reversing a player's death. After death, the game will erase the save game. However, if you pause the game right after you are killed and before the next menu pops up, you may then force quit and restore your last save game in the run. This was the only way less skilled players were able to finish the game with The Lost.

Of course, this method when abused does take away the charm and fun from the game, not to mention significantly extending the real-time it takes to get through a run. A half-hour game may easily extend to several hours if one tries to Force Quit repeatedly.

In Afterbirth, the Force Quit method has been partially patched. It still works as in Rebirth except after a player's death. If you attempt to Force Quit after death, the continue option is not selectable, and you have to start a new game.

Having extra lives used to allow the Force Quit method to work after death. There was no need to immediately pause the game after a death in this case. Force quitting after the extra life starts would still restore the last save game. This has since also been patched.

Alternatively on OS X and Windows, one may disable cloud saving and copy / restore certain save files after quitting the game. This is capable of reversing a player death and allow less skilled players to finish The Lost and Keeper runs. However, this is risky and careless copy and pasting may result in permanently lost in-game achievements and secrets. One does not need to force quit either and may close the app normally. BACK UP YOUR SAVE FILES before attempting the following.

Go to The Binding of Isaac Afterbirth folder. Find options.ini and open in a text editor. Change the SteamCloud value from 1 to 0. Save the change to options.ini.
When SteamCloud is disabled, the local save file will not reflect your latest cloud save file. The game will look like you're starting from scratch. You can use your last local copy of the cloud save file as the new local save file. The cloud save has format [YearMonthDate].ab_persistentgamedata[Slot#].dat. Rename this file (and overwrite) to persistentgamedata[Slot#].dat. For example, if using slot 1, rename 20160331.ab_persistentgamedata1.dat (and overwrite) to persistentgamedata1.dat. Now your local save file will reflect your last cloud save file.
Play the game and reach a point where you want to save. Pause and exit to the menu to generate a save file (alternatively, starting a new level will generate one). Look in the Binding of Isaac Afterbirth folder for 2 specific files with the following formats: gamestate[Slot#].dat and persistentgamedata[Slot#].dat. Copy these files to another folder on your hard drive. For example, if using slot 1, copy gamestate1.dat and persistentgamedata1.dat to another folder.
Since you are using this method and are going to screw up, you may exit the app normally after your character dies instead of force quitting. You'll notice that gamestate[Slot#].dat has disappeared from the Isaac folder. Restore the gamestate[Slot#].dat and (overwrite) persistentgamedata[Slot#].dat files from your other folder.
Restart the app. You'll notice that the continue option is now available. You may resume your failed run.
In-game and Steam achievements will still unlock with this method.
Once you are done manipulating files and want to go back to Steam cloud saving, go back to options.ini in the Isaac folder and change SteamCloud value back to 1.
However, once you do this, your cloud save is the old one. To update your cloud save with your current local save, copy the persistentgamedata[Slot#].dat file from the Isaac folder to the remote folder. Rename (and overwrite) to ab_persistentgamedata[Slot#].dat. For example, if using slot 1, copy persistentgamedata1.dat from the Isaac folder and rename/overwrite to ab_persistentgamedata1.dat in the Remote folder.

This can also work on the 3DS by pausing just as you die and pressing the home button, then closing The Binding of Isaac. Reopening the game and hitting continue will respawn you on the floor you died on. This will reset your progress for that floor. This can be repeated as much as needed; however, there is a bug. If used on the first floor, and the character that dies spawned with any active items - such as Isaac's D6, The Lost's D4, or Judas' Book of Belial - the items will be removed. This can be fixed simply by quitting and continuing whilst still alive.

The Binding of Isaac: Rebirth