I'm right-handed and don't have particularly good manual dexterity with my left. I find I can still work the Cryo open and closed one handed without difficulty (or injury) using my left hand. The handle is wide enough and the frame lock thick enough to where I can get a good grip on it and pull it out of the way with my left thumb. The torsion bar also keeps the blade from closing too far without deliberate force, so I don't accidentally snap it shut on my fingers. So, for actual lefties, I'd imagine the Cryo would be pretty easy to use.