After getting Skatole (that's the poop that makes all the flies love you), is it possible to get another useful item if you find a second Skull Game guy on the same playthrough? Or will it be an endless loop of keys, bombs, hearts, etc?
3 Answers
The Skatole is the only significant item you can acquire from the skull game. After getting the Skatole, it's an endless loop of coins, hearts, keys, and bombs. Also the occasional fly, which won't be an issue if you have the Skatole.
From the Binding of Isaac Wikia:
Shell Game: Bet 1 coin and a bomb, heart, key, coin, or the grand prize of Skatole is put under a skull and the skulls are shuffled in a manner impossible to follow.
This is also based on my repeated playthroughs.
The wiki page for the arcade lists only Skatole as an item that can be received from the skull game, and this is consistent with my observations. I have at times gotten the Skatole and then played the next skull game through dozens of wins without getting anything besides pick ups.
As others have already said, Skatole is the only "final" item you get from the Shell game.
Any other instance of the arcade wil give the other lesser items, and the game won't disappear.
It should be noted anyway that with the Lucky Foot (Cain's starting item) you get a 50% winning chance at the Shell game, instead of the usual 33%, so it can be a good source to replenish all your items, using it in combination with the Blood donation machine and the Slot.