The Blindfolded condition was originally exclusive to the Solar System, Cat Got Your Tongue, Beans!, and The Family Man challenges. Afterbirth added several challenges (Blue Bomber, BRAINS!, and The Guardian) and the character Lilith also use the blindfold condition. Currently, The Blindfold is unobtainable.
- The blindfold prevents Isaac from firing tears and other firsthand sources (e.g., Mom's Knife and Dr. Fetus.
- Because it is not an actual item, Isaac can not get rid of it by Dice Rooms, Missing No., The D4, or The D100, and it does not show up on the "My Stuff!" screen.
- Although he can not fire tears himself, he can still command familiars to attack and use active items.