Aprils Fool is Challenge 32. Isaac has no special starting items for this challenge. However, all floor bosses are changed to The Bloat, Stonies have a chance to be replaced by Cross Stonies, all Items, Trinkets, and Pickups display an incorrect sprite, activated items and pickups never activate the correct effect, and Isaac's location is displayed as a random room on the map. The goal is to defeat Mom's Heart, which has also been replaced by The Bloat. Treasure rooms and Shop rooms are present in this challenge.
- All changes mentioned above are designed to make this challenge exceedingly difficult and frustrating.
- While Curse of the Blind is not active, the fact that all pedestal items are displayed incorrectly means that, like with Curse of the Blind, it is impossible to know what each item is until acquired.
- All items are still pulled from the correct Item Pool (Angels will still drop Key Pieces, Mom will drop The Polaroid and The Negative if they are unlocked).
- Pickups (coins/hearts/bombs/keys), unlike pedestal items, are not displayed incorrectly. Once a pickup is acquired, it is randomly changed to another.
- Coins and keys give hearts, bombs or keys.
- Bombs give hearts, coins or keys.
- Hearts give coins, bombs or keys.
- This makes it very hard to accumulate coins as they can be gained only from bombs and hearts, at a 1 in 3 rate.
- All active items, pills, cards and runes have a random effect upon being used. This makes any strategy involving them unreliable and potentially dangerous. Cards can trigger the Suicide KingKills Isaac and spawns lots of pickups, items, and/or chests in the same room. effect, pills can activate the Health Down effect, and active items can trigger Plan C.
- Cross Stoneys are significantly more challenging compared to regular Stonies.
- Most importantly, every single boss found during the challenge is The Bloat, which is normally found as early as Chapter 3. As a result, the boss fights before Chapter 3 will be more challenging than usual.
- Randomness is a major source of difficulty in this challenge, but it can also be the key factor to completing it, as sometimes coins will grant Soul Hearts, Black Hearts, and Gold Hearts. If a large number of coins are found in one place, it is possible to dramatically increase Isaac's health pool. Gold hearts, in particular, are useful, as they can spawn a large number of coins when depleted, which in turn can be used to grant a large number of other pickups.
- When dimes or nickels are picked up, they will grant 10 or 5 of the pickup they act as respectively, which can lead to incredibly powerful results, such as acquiring 5 gold hearts at once.
- It is possible to use a Swallowed PennyUpon taking damage, Isaac drops a penny. along with a sacrifice room to generate infinite coins, assuming Gold Hearts are repeatedly spawned in the process. This also will trigger many of the sacrifice room's effects, notably transporting Isaac to the Dark Room. The challenge can still be completed by defeating The Bloat at the end of the Dark Room stage. This can be done as early as the first floor, allowing most of the Bloat fights to be skipped entirely.
- Active items with a short charge time, such as Butter Bean, or no charge time, such as Kamikaze!, can allow for rapid use of random active item effects. While this can be extremely powerful if lucky, this can also trigger effects like Plan C, killing Isaac.
- The map always displays Isaac's location incorrectly, randomly selecting a room on the floor for this purpose. As this includes rooms not yet uncovered through traditional methods, it is possible to learn Secret Room locations from this.
- Counterfeit PennyGives a 50% chance of increasing the value of every coin pickup by one. has a chance to grant coins upon picking them up, making it easier to accumulate coins.
- Pills will always show their true effect in their name after being used, and the narrator will always state what the effect is, meaning that setting the narrator to always activate can be helpful.
- Using the Book of Revelations can replace The Bloat with a Harbinger.
- It is possible to get repeats of the same item during this challenge.
- When encountering a Double Trouble Boss Fight, The Bloat will not appear.
- Lucky Pennies will still grant the boost to Luck but will be otherwise randomized as usual.
- It is possible to go to The Void during this challenge. However, The Bloat will appear instead of Delirium, making the challenge unable to be completed.
- This challenge's effect of changing item appearance is similar to the April Fool's 2016 daily challenge.
- The Bloat's appearance as a replacement for all other bosses is a reference to the exceptional hatred some fans express toward this boss.
- The user who suggested this challenge was banned from a subreddit (NSFW) whose theme is hatred towards The Bloat. This same user was also forced to use the "I love The Bloat" flair for a week on the Binding of Isaac subreddit. 
- Cross Stoneys are exclusive to this challenge and were added in Booster Pack #5.
- Ironically, Cross Stoneys were revealed on April 1st. 
- Similarly to The Bloat's inclusion in this challenge, Cross Stoneys are a nod to the community's generally negative reaction to Cross Stone Shooters added in the previous booster pack.
| Mom Unlocks
|The WombDefeat Mom for the 1st timeThe HarbingersDefeat Mom for the 1st timeA Cube of MeatDefeat Mom for the 1st timeA HaloDefeat Mom using The BiblePuristDefeat Mom for the first time
||XXXXXXXXLDefeat Mom for the 1st timeSPEED!Defeat Mom for the 1st timeHave a HeartDefeat Mom for the 1st timePRIDE DAY!Defeat Mom for the 1st timeOnan's StreakDefeat Mom for the 1st timeThe GuardianDefeat Mom for the 1st time
||Aprils foolDefeat Mom for the 1st time