- Sister Maggy
- Skatole
- Skeleton Key
- Slot Machine
- Sloth
- Speed Ball
- Spelunker Hat
- Spider
- Spider (disambiguation)
- Spider Bite
- Spider Butt
- Spikes
- Spirit Of The Night
- Spit
- Spitty
- Spoon Bender
- Squeezy
- Stats
- Stats/Damage
- Stats/Health
- Stats/Hidden Stats
- Stats/Range
- Stats/Speed
- Stats/Tears
- Steam Sale
- Steam Trading Cards
- Stem Cells
- Steven (boss)
- Steven (item)
- Stigmata
- Stone Grimace
- Sucker
- Super Bandage
- Super Envy
- Super Gluttony
- Super Greed
- Super Lust
- Super Pride
- Super Secret Room
- Super Sloth
- Super Wrath
- Swarmer
- TNT Barrel
- Tammy's Head
- Tarot Cards
- Tear
- Technology
- Technology 2
- Telepathy For Dummies
- Teleport!
- Teratoma
- The Basement
- The Battery
- The Bean
- The Belt
- The Bible
- The Binding of Isaac
- The Binding of Isaac: Afterbirth
- The Binding of Isaac: Eternal Edition
- The Binding of Isaac: Rebirth
- The Binding of Isaac: Unholy Edition
- The Binding of Isaac: Wrath of the Lamb
- The Binding of Isaac: Wrath of the Lamb/Bugs
- The Binding of Isaac (Merchandise)
- The Binding of Isaac (OST)
- The Binding of Isaac (music)
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