Tainted Isaac can only hold 8 passive items at a time. Tainted Isaac's current 8 passive items are visible in the top-left corner of the screen, with one highlighted by a white square. Upon picking up a 9th passive item, the item currently selected, or rather the item currently in the white square, will be dropped on a pedestal in front of Tainted Isaac. The swap key can be pressed to cycle which item is selected.
In exchange for this, all rerollable item pedestals, Shop items, and Devil deals will cycle between two items for the player to choose from, essentially a stronger version of More Options + There's Options. Whichever item is currently visible when the item is picked up will be the one selected. Once an item has been picked up it will no longer cycle between items.
Dropping items causes their passive buffs to be removed, however health or pickups will be kept (such as fromBreakfast or Pageant Boy). Note that pickups will be kept regardless of which way they were gained (picked up or directly added to the counters).
Even if one of the item is a set drop, the other one is still randomly pulled from the current room's item pool.
Some passive items can be taken and left behind without their effect being reverted, such as HP upgrades like Breakfast. They should be left behind as a priority. Many items not having their effects reverted are listed in Synergies and Interactions section.
Stat changes from Pills are permanent. This can make them either extremely useful for stats allowing less stat up items to be held on to and make more room for other items or extremely detrimental as Tainted Isaac cannot counteract stat downs with items as easily due to only being able to hold eight items.
Transformations, including incomplete transformations, will not be reverted when items contributing to them are left behind.
In Co-op mode, the other character can pick up the items that Tainted Isaac drops but this item will no longer contribute to the transformation it is a part of.
Killing the Boss of a floor in Co-op mode will spawn a Boss item that cycles between two different options, but any subsequent options will not come with an extra choice.
If using the D4 or D100 or D Infinity to reroll passive items, careful use can use these to accumulate heart containers in a way other characters can't. Tainted Isaac doesn't lose heart containers when he drops a health item for a full inventory (unlike when health items are rerolled), so he can reroll to gain a health item and if he drops it instead of rerolling it the extra health persists, making it easier for him to accumulate more health containers.
Cards like XIV - Temperance or XX - Judgement can be extremely powerful, as they allow to spawn an item from a specific item pool. For example, donating to a Blood Donation Machine will spawn either Blood Bag or IV Bag and cycle with a second item pulled from the current room item pool. This can be used to get powerful items from Angel / Devil Room, or help in completing the collection page if the player wishes to avoid a full game break (such as using Tainted Cain or D20) and is actively looking for items in a specific pool.
Due to the limited amount of items, Trinkets have a more important role with this character. Therefore any item helping to gain some, such as Mom's Box, will help a lot. Items or pickups that allow to absorb them (Marbles, Smelter, Gulp!...) are even more important.
Abyss: and Void are extremely powerful with Tainted Isaac. Any item left behind (especially health ups and items that give one-time effects such as Booster Pack) can be consumed for stat upgrades or red attack locusts.
Birthright: Gives Tainted Isaac four more item slots without taking up an item slot itself.
Birthright can be rerolled by items such as the D4, but it will only partially undo the effect of Birthright. If you had more than 8 items at the time of reroll, the extra items are retained above the usual limit. These extra items do take full effect, and can be rerolled, but are not displayed and cannot be selected to drop next in the set of items. Collecting Birthright again will show these extra items.
Brittle Bones: The tears upgrades will not be reverted when left behind.
Butter!: When Tainted Isaac drops his active item, it is considered a "new pedestal," this means that the item will be given a second option, but it also fully charges the active item. It's considered a new Pedestal each time it drops, which means you can dig through an item pool for the exact item you want, assuming you're willing to drop your active item for it.
This synergy also allows for infinite (albeit slow) usage of any active item.
Candy Heart: The stat upgrades will not be reverted when left behind.
Death's List: The stat upgrades will not be reverted when left behind.
Eden's Blessing: Grants a random item at the start of your next run, even if you are to drop it and not finish your run with it.
Knife Piece 1, and Knife Piece 2: As they do not take up inventory space (even after combining into the Knife familiar), they allow Tainted Isaac to gain extra damage without taking up any inventory slots.
Lost Soul: Respawns after being hit if swapped for another item and picked back up again, virtually guaranteeing rewards as long as Isaac's inventory is full.
Lucky Foot: Can help Tainted Isaac build up a large amount of stat boosts via pills without having items tied to them.
PHD: Can help Tainted Isaac build up a large amount of stat boosts via pills without having items tied to them. Dropping it will make pills effects back to normal, but pills will remain identified.
Redemption: The damage upgrades will not be reverted when left behind.
Schoolbag: If it is dropped from the inventory when Tainted Isaac is holding two active items, one of those active items is also dropped, generating another item pedestal. This new pedestal cycles between the dropped active item and another item from the current room's pool. Tainted Isaac can take Schoolbag and the active item again, and repeat the process indefinitely. This can be used to look for specific items in a given item pool, allowing for an easy way to get powerful items, such as Mom's Knife or Godhead, if done enough times.
If Remote Detonator is dropped in this way, Tainted Isaac's bombs will no longer explode unless the item is picked up again and activated, making player's bombs useless without this item held.
Soul Locket: The stat upgrades will not be reverted when left behind.
Virgo: Can help Tainted Isaac build up a large amount of stat boosts via pills without having items tied to them.
XX - Judgement?: Allows Tainted Isaac to deplete the current item pool faster (given full inventory) when an item pedestal is present.
With Sacred Orb combined, powerful items can be obtained way more easily.
Binge Eater: The stat upgrades will disappear if it or the food items are left behind. The temporary damage up will not be reverted, but will still decrease over time as normal.
Book of Virtues: Is considered a passive item by the game and will take up one of Tainted Isaac's inventory slots.
Cambion Conception: Familiars granted will not take up inventory slots, but will disappear if those items are left behind and will not be regained if Isaac picks them up again.
Crooked Penny: Makes each copied pedestal rotate between the item that was on each pedestal at the time it was used and a random second item.
Diplopia: Makes each copied pedestal rotate between the item that was on each pedestal at the time it was used and a random second item.
False PHD: Dropping it will make pills effects back to normal, but pills will remain identified. Damage upgrades will disappear if it is left behind, but will remain tied to the item and can be picked back up again. This will not, however, revert back the decreased stats.
GB Bug: When his inventory is full, he is able to swap it with another item from a pedestal. Every time GB Bug is picked up, the familiar will be re-summoned even if a room has not been cleared since the last re-roll. This allows Tainted Isaac to re-roll pickups indefinitely until they become chests, increasing the amount of pickups or giving items. However, the pickups may also re-roll into troll bombs, effectively removing a pickup to re-roll. This can be mitigated by having Safety Scissors.
Keeper's Sack: The stat upgrades will disappear if it is left behind, but will remain tied to this item. If Isaac picks it up again, he will regain them. Dropping bought items will not remove the stat upgrades gained by buying them. If Isaac buys an item and it results in him dropping Keeper's Sack, he will not get any stat upgrades from buying it.
Missing No. can be dropped when Tainted Isaac's inventory is full, which makes it easier to get clear benefit from than other characters. Tainted Isaac can carry from floor to floor until he rolls a useful combination of items, and then can choose to drop it so that it doesn't reroll his items on future floors.
0 - The Fool?: May spawn coins and/or bombs as pedestal items such as Boom! or A Quarter, however these pedestals won't cycle between two different items.
Rock Bottom: Prevents any stat from decreasing, letting the effects of picked up items linger even after discarding them. However, raising stats beyond the values reached will be more difficult after leaving the source item, and swapping away Rock Bottom resets them to Tainted Isaac's current set.
Vengeful Spirit: Wisps will remain until the end of the floor if the item is left behind.
The achievement for unlocking Tainted Isaac is "The Broken". This is the name used in The Binding of Isaac: Four Souls.
Tainted Isaac's unlock for Ultra Greedier is the XVII - The Stars?. Typically, this card symbolizes a lack of faith and despair. This is probably a reference to the fact that Isaac is shown to view himself as evil, and believing his only escape out is to end his own life.
Tainted Isaac's transition screen portrait.
If a Clicker is used to switch to Tainted Isaac, the game will crash even if they have less than 8 items.
If Isaac picks up an item, quits to the main menu, and then continues the run, this item will not be displayed in Isaac's 8 item slots but will be displayed on the hud. It's only a visual bug and Isaac still has this item. Pressing control should fix this.
Starting a run as Tainted Isaac after acquiring more than 8 Eden's blessing's in a previous run will cause the game to crash.
If Bag Lunch or Wish Bone are triggered to create an item at any point while playing as Tainted Isaac, item pedestals will be permanently altered until the entire game is quit, i.e. the program is closed. In some cases, item pedestals may not cycle between items at all or require leaving and reentering the room to begin cycling. In addition, any proceeding item pedestals that switch between two items will do so even if one has already been taken after refreshing the room. With a full inventory of items (and thus the ability to place items in other items' place), this effectively allows Isaac to reroll for any desired item.
If the player replaces Tooth and Nail while in its invulnerable state, the player will remain invulnerable for the remainder of the room.
Sometimes, items generated by TMTRAINER can bypass Tainted Isaac's item limit. Attempting to pick up a non-glitched item with a glitched item selected for replacement will add the normal item to Isaac's permanent inventory.
Sometimes item pedestals don't cycle as they should, exiting and continuing the run should fix this.