Some bosses have special interactions with this item:
Attempting to use this item to kill Delirium or Mother will not work. Their death animation is much longer than the time between using Plan C and Isaac's Last Will appearing, meaning Isaac will die first and it will not count as a kill. Having extra lives that revive Isaac outside the room will not help, either; they must be fought again.
However, items that revive Isaac in the same room he died in, namely Lazarus' Rags (or being Lazarus), Inner Child, Soul of Lazarus, and Tainted Lost's Birthright, will allow Isaac to bypass this and kill them with this item. In the case of Lazarus' Rags, though, the completion mark will go toward Lazarus and not the character originally selected.
Similarly, if playing as Tainted Lazarus, using Plan C and then using Flip to switch to the other form pauses the death counter until the player switches back to the form that originally used the item.
It is possible to kill Delirium by carefully timing pauses after each screen static. Each screen static plays a cutscene that continues to play even while paused, so by pausing and unpausing at the right timings, Delirium's death animation can be shortened to just under 3 seconds allowing for his completion mark to be awarded.
Using the effect of Plan C while Isaac is already under the timer of Plan C (such as through the use of another Plan C, ? Card, Wild Card, ect.) will reset the timer each use, allowing to stall bosses with long death animations.
Killing Mother's second phase with Plan C will kill Isaac just at the end of her death animation. No completion mark is awarded.
However, if Isaac is revived outisde the boss room, the boss will be considered dead and the mark will be awarded. This does not work for The Lost, Tainted Lost, The Forgotten (when playing as The Soul), and Tainted Forgotten since ghost characters have a slightly shorter death animation.
Killing Ultra Greed's second phase with Plan C will give a completion mark, with the exception of The Lost, Tainted Lost, The Forgotten (when playing as The Soul), and Tainted Forgotten. This is because ghost characters have a slightly shorter death animation, resulting in Isaac's Last Will appearing more quickly.
If used in The Beast battle, Plan C will only kill the harbinger that Isaac is fighting on screen. It won't have any effect on the other harbingers nor The Beast itself (The Beast can still be killed if Isaac is fighting it when Plan C is used, and there is enough time to earn the completion mark).
It is recommended not to use this item in Challenges, as even if the goal is within the bosses that dies before Isaac does, the player will likely die before the end of the rising trophy animation.
For the game's sake, a run is not truly over until Isaac's Last Will appears. This means that some bosses that might seem to finish their death animations after Isaac dies, such as Ultra Greed, will still be technically killed and will still give their completion marks, even if Isaac does not enter the Final Boss Chest.
Invulnerable enemies and closed Hosts will not be killed by Plan C.
Isaac's last will shows his last damage source as the cause of death, not Plan C. If Isaac has not taken damage or lost health from any source, Isaac's face is shown.
Invincibility or the Holy Mantle shield will not save Isaac from being killed.
Some items that activate when Isaac reaches zero hearts, such as Heartbreak and Spirit Shackles, will not activate, killing Isaac.
Even if Isaac enters a trapdoor immediately after using Plan C, he will still die after arriving at the next floor.
Isaac will also die after accepting a Victory Lap or performing a RERUN.
Plan C has an 80% decreased item pool weight, making it less likely to appear than other collectibles.
Book of Virtues: Spawns 8 red wisps that shoot red tears at 12 damage per tear. Using Plan C will kill Isaac as expected, but wisps won't disappear if used with an item that grants an extra life.
Multiplayer: Only the player who uses Plan C dies.
If the user dies from other causes before the effects of Plan C can conclude, their ghost will die, resulting in a run loss, regardless of there being other players alive.
This item is a reference to abortion pills, which are commonly given the nickname "Plan C." ("Plan A" being typical birth control methods, and "Plan B" being the so-called "morning-after pill," which prevents pregnancy in cases where contraception has failed.) The item's mechanic is a reference to abortion terminating an unborn fetus.
The Lamb, 
Hush, 
Ultra Greed, 
Mega Satan, 
Mother, and 
The Beast.
Delirium or 
Lazarus' Rags (or being 
Lazarus), 
Inner Child, 
Soul of Lazarus, and 
Tainted Lost's 
Birthright, will allow Isaac to bypass this and kill them with this item. In the case of Lazarus' Rags, though, the completion mark will go toward Lazarus and not the character originally selected.
Tainted Lazarus, using Plan C and then using 
Flip to switch to the other form pauses the death counter until the player switches back to the form that originally used the item.
? Card, 
Wild Card, ect.) will reset the timer each use, allowing to stall bosses with long death animations.
The Lost, 
The Forgotten (when playing as The Soul), and 
Tainted Forgotten since ghost characters have a slightly shorter death animation.
Killing 
Hosts will not be killed by Plan C.
Holy Mantle shield will not save Isaac from being killed.
Heartbreak and 
Spirit Shackles, will not activate, killing Isaac.
Plan C is found in 6 item pools, the second highest count amongst all items, behind 
Cube of Meat. Its lowered weight, however, offsets its presence.
The Book of Belial + 
Judas / 
Dark Judas: Respawns Judas as 
Book of Virtues: Spawns 8 red wisps that shoot red tears at 12 damage per tear. Using Plan C will kill Isaac as expected, but wisps won't disappear if used with an item that grants an extra life.
Car Battery: No effect.
Forget Me Now.
Pill Items 
Lazarus Unlocks 
Ultra Greedier Unlocks 
The Binding of Isaac: Rebirth
