Isaac's Tears 
Effects
- Each tear shot by the player increases item charge by one.
- Upon use, fires 8 tears around Isaac, which retain the damage, range, shot speed, and most special tear effects.
Notes
- The effect of
Tammy's Head is similar to Isaac's Tears, but Isaac's Tears will not benefit from tear-replacing items like 
Brimstone.
- (Removed in Afterbirth †) It takes 1.3 seconds to use, during which time Isaac cannot shoot tears normally. Because of this it is only worth it to use Isaac's tears DPS-wise if 4 or more tears successfully land.
- (Added in Afterbirth †) It takes 0.4 seconds to use, during which time Isaac cannot shoot tears normally.
Synergies
- (Added in Repentance)
Book of Virtues: Summons six wisps at a time, in the middle ring. Using Isaac's Tears destroys the previous set of wisps. The wisps are automatically destroyed after three seconds.
Interactions
- (Removed in Repentance) Brimstone /
Mom's Knife: The item fires normal tears, although it will charge nearly instantly while the attack charges.
- Brimstone + (Added in Afterbirth †)
Lachryphagy: When tears burst, they will shoot out Brimstone lasers in a fashion similar to Tammy's Head.
- (Added in Repentance) Brimstone: Rapidly charges Isaac's Tears, while firing, instead of charging.
- (Removed in Repentance)(Added in Afterbirth)
Car Battery: No effect.
- (Removed in Repentance)
Chocolate Milk: The size and damage of tears fired depend on how far Isaac has charged up his shot. For example, if Isaac has completely charged his shot, the tears fired by the item will be fully charged.
- (Added in Repentance) Chocolate Milk: Charge does not have any effect on the damage of the tear, but will still be colored like Chocolate Milk tears.
Dr. Fetus: Fires normal tears.
Epic Fetus: The item fires normal tears, but charges very quickly as the crosshairs are moved.- (Added in Repentance)
Eye of the Occult: Generates a halo of tears that don't break their shape. This lets you easily get the most out of every tear generated by Isaac's Tears.
- (Removed in Repentance)
The Ludovico Technique: The item charges based on the tear's movement.
- (Added in Repentance) Mom's Knife: Charges the item like normal.
- (Added in Afterbirth † / Removed in Repentance)
Schoolbag: When Isaac's Tears is in the first active item slot, the secondary item does not charge upon clearing rooms.
- (Added in Repentance)
Spirit Sword: The item fires normal tears and can be charged as fast as the sword can be swung. Doing a spin attack will fully charge Isaac's Tears.
Technology: Fires normal tears.
Technology 2: Fires normal tears.