Best Friend: Spawns two decoys on top of each other.
Blank Card: Uses the card twice. For example, if used with the Two of Hearts/Diamonds/etc. cards it will quadruple whatever amount Isaac has.
Blank Card + Tarot Cloth: The effect of the active card is quadrupled.
Broken Shovel: Prevents the Mom's Foot from appearing for two rooms (empty or not), or for two waves of a Challenge Room or the Boss Rush, essentially removing the stomping attacks for the entire duration of the Boss Rush.
Isaac's Tears: The damage of tears shot from the active item is doubled.
Kamikaze!: Now causes smaller explosions in a ring around Issac.
Jacob's Ladder / 120 Volt: Electricity deals 75% of Isaac's tear damage if he owns 1 of these items, to 100% if Isaac owns both.
Crooked Penny: Splits the 50% chance to succeed into a 25% chance to quadruple all items and a 25% chance to duplicate all items while consuming the originals; the latter will make Devil deal and Shop items free.
The 25% chance to duplicate all items while consuming the originals now generates 2 pennies instead.
Sulfur: Will count as giving double Brimstone, giving extra damage and a x1.2 damage multiplier for the current room.
Void: Applies Car Battery's effect on all eligible absorbed active items. Absorbing passives will not give extra stat ups.
Clicker: If the Car Battery is removed by the first activation, a second activation will not happen. Two activations in a row is mostly detrimental, removing two items and possibly cycling through a character that lowers health.
Dark Arts: Doubles the duration, giving more time to walk through more enemies, if you end the effect before the end of the first second, the item will reactivate itself; allowing to target the same enemies twice.
D4/D100: Instantly re-rolls Isaac's items twice, which doubles the speed at which the item pools are exhausted and transformations are achieved.
As items are returned back into the item pool when re-rolled, the item pools aren't exhausted at all. In addition, you need to actively be holding a transformation's respective items to retain them now, so using the double re-roll to gain multiple transformations is no longer possible.
The D6/D8/D12/D20: Re-rolls twice instantly without any benefits. The D6 depletes item pools at double the speed.
D12: Roughly doubles the rare chance of obstacles being turned into Reward Plates, Killswitches, and very rarely Crawl Spaces, as the D12 can create these but cannot re-roll them.
D7: Doubles the amount of enemies summoned, but does not give double rewards.
D infinity: Activates 2 dice. The second activation die cannot be predicted.
Activates the currently selected die twice.
Dull Razor: The invulnerability time is not increased, but damage-triggered items will activate twice if applicable.
Eternal D6: Re-rolls twice like The D6 (see above), but the 30% chance of the item disappearing is increased to 51%.
Everything Jar: Instead of doubling its effect, Everything Jar will spawn a poop alongside its normal drop.
Guppy's Head: Increases range of flies spawned to 4-7.
Head of Krampus: Doubles the damage the brimstone beams deal (for a total of 880 damage/ 400 damage per use). Doesn't double the brimstone beams' duration.
Metronome: Metronome is activated twice at once as expected, but the item chosen for the first activation is shown raised above Isaac's head, instead of the second one that actually remains active.
Moreover, active item effects chosen by Metronome are only activated once.
Mine Crafter: Spawns a Movable TNT and instantly detonates it, damaging Isaac.
This has been changed to spawn two Movable TNT barrels instead, which you can detonate at will.
Moving Box: Activation swaps the contents of the box with the contents of the room.
This has been changed to have have no effects.
The Scooper: Will summon 2 peepers in a bifurcated direction.
Spider Butt: Deals 10 damage to enemies twice but does not increase slow effect.
Stitches: Swaps places with Isaac twice in quick succession, rendering Stitches useless for collecting pickups & items beyond pits, rocks etc.
However, it can still be used to telefrag enemies.
Tear Detonator: Multiplies detonated tears, resulting in 6x more tears than normal.
Telekinesis: Grants 7 seconds of protection, effectively giving Isaac immunity to enemy bullets as long as the item is used immediately upon recharging.
171 activated items, 45% – 77 items – are not eligible.
Bug!
Mr. ME!: Grabbed items and pickups may become ghostly and impossible to pick up. Leaving the room and returning fixes this.
Active Item Modifiers 
Batteries 
The Binding of Isaac: Rebirth
