Ever since I got the chained takedown skill, I've been using it almost exclusively for close-quarters stealth combat. I can't always get it to work reliably, though. There are times when I'll be able to whirlwind through a room destroying everyone, and there are times when the second or third guard I try to chain will be able to knock out my combo.
I think it has something to do with alertness, but I've definitely gotten the "ding!" alert noise before and still been able to chain the takedown of that guard.
What determines whether a chained takedown will work on an enemy?