- Once activated, all tears in the air split into 6 more tears in all directions, which retain their damage, and shot speed.
- Akeldama: Will bust tears generated by Akeldama into Isaac's current tears.
- Angelic Prism: Tears that are split by the prism can be split again by Tear Detonator.
- Anti-Gravity: All tears currently floating in the air will be multiplied, resulting in a massive amount of tears.
- Book of Virtues: The wisps' tears are also detonated; the resulting tears are based on Isaac's own, rather than the wisps'. Created wisps have a chance to trigger Tear Detonator's effect when destroyed.
- Car Battery: Multiplies the tears, effectively creating dozens of tears.
- Compound Fracture/ Cricket's Body/ The Parasite: Tears that are split can split again into burst tears.
- Haemolacria: Splits tears into 6 Haemolacria tears that burst into split tears. If split tears are burst, all of them will split into 6 Haemolacria tears creating an enormous amount of tears when the main tear splits again.
- Ipecac: All tears will split into 6 explosive tears, making it very powerful (but also dangerous unless Isaac has Host Hat or Pyromaniac).
- Lachryphagy: Similar to the Haemolacria synergy, if the main tear splits, 6 tears will spawn that can be fed. However, if burst tears are split, all burst tears will split into 6 tears resulting in an enormous amount of tears that are likely to feed each other.
- Lead Pencil: Each of the tears explodes into 6 smaller tears.
- The Ludovico Technique: The tear explodes into six smaller tears, then reappears next to the player.
- My Reflection: The shrapnel tears will curve back to the location of the original detonated tear.
- Sad Bombs: Bomb tears are multiplied.
- Shooting familiars: Shooting familiars' tears explode into Isaac's tears, with his actual damage and effects.
- Tiny Planet: Tears split, and then orbit around where the tear was originally from, three spinning clockwise, three counterclockwise.
- Trisagion: Tears split into six beams.
- Chocolate Milk: No matter how charged the tears are, split tears always deal a tiny amount of damage.
- Explosivo: Tears that are stuck to enemies will not deal explosion damage; tears released by it may be sticky tears that immediately stick back onto the enemy.
Tear Detonator becomes useless with the following, barring other sources of tears:
PC P0J3 YNW0 (First Floor's Tresure Room)
|The Binding of Isaac: Rebirth|
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