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I thought these opened if you have full health. I actually had full + 2 blue hearts before dropping a bomb on myself before taking the screenshot.

But even here I have full health... right?

enter image description here

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up vote 6 down vote accepted

This is a boss challenge room, not a regular challenge room. You can tell there is a difference because on your minimap, there is a bit of blood on the sword and the skull above the door.

In order to enter, you must have one heart or less remaining (not including the blue hearts)

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In addition to the blood on the sword, there's a skull above the door, while a normal challenge room just has the crossed swords. – Kappei Dec 9 '13 at 8:22
@Kappei Thanks for that. Added into my answer. – aman207 Dec 9 '13 at 16:20
Also, note that you will fight two waves of bosses, rather than 3 waves of generic enemies. This includes Larry Jr.'s, Peep, and Chub, primarily. (In places like the Womb or Cathedral, a regular challenge room will uses bosses as well) – Kyle Baran Oct 27 '14 at 22:32

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