Isaac dies if he has a single heart container and an Eternal heart then makes a deal costing more two or more hearts. Without any heart containers, the gameplay functions exactly like ?, making red hearts and red heart-related items useless until more heart containers are obtained, along with other special effects such as Whore Of Babylon always being active. 
If the player has Soul Hearts and buys an item for exactly as many red heart containers as they currently have, Isaac will keep his Soul Hearts. If the player only has Soul Hearts and have less than three Soul Hearts Isaac will die. If the player has Soul Hearts and buys an item for more red heart containers than they currently have, Isaac will lose all heart containers and Soul Hearts, and will die from a single hit until more Soul Hearts or heart containers are collected. In Rebirth Devil Rooms can be extremely game breaking as the player can remove all red heart containers in order to buff certain items such as the Whore of Babylon, The Polaroid and The Negative similar to how these items normally act for ?. This does not happen in Rebirth if the player has any soul, shadow or eternal hearts. If the player has no Soul Hearts and buys an item for exactly as many or more red heart containers than they currently have, Isaac will die. When playing as ? or any characters without any heart containers upon entering the room, all items will cost 3 Soul Hearts. 
You can still take damage if you have Soul Hearts, but all Soul Heart damage taken lowers the chance of the room appearing slightly.
In Rebirth, the simplest way to unlock the Devil Room is to simply take no red heart damage throughout the entire level (this includes damage from enemies, projectiles, spikes, etc).
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