Upon activation all pickups in the room (e: pills, coins, keys, bombs) will randomly change into another pickup item, even undetonated troll bombs. The D20 can even help in combat as it will turn War's troll bombs into many pick-ups. The D20 can also reroll opened chests that have already been raided. This item, unlike The Dice, is not able to reroll collectibles.
- Any item able to spawn a sufficient amount of pickups to transform, such as Pageant Boy or the IV Bag.
- The Habit can be used to abuse the Blood Donation Machine inside Arcade rooms along with the D20 to reroll large amounts of unwanted items such as simple pennies repeatedly from the Arcade facilities, and likely receive enough hearts and Soul Hearts on top of the loot to repeat the process ad nauseam.
- The D20 is also effective if used quickly with the bombs from the Anarchist's Cookbook or The Tower, as they are also changed into other pickups.
- Already opened chests can be rerolled if there is no item above them. Do note that opened chests disappear after leaving the room.
- There is a hard limit of pickups that the D20 will reroll in a single use (around 30).
- If D20 is used right after a coin is collected, the coin (with disappearing animation) will be also rerolled, so you can get both.
- Unlike the D6, the D20 cannot reroll pickups that are for sale at the shop.
- The item's effect is similar that of The Dice.
- It may be a reference to Dungeons & Dragons, a popular tabletop role-playing game which uses a 20-sided die.