It makes a massive difference in comfort. 5 minutes typing at full speed on QWERTY and my wrists start to hurt. (I really don't know how people do it.) On Dvorak, I can type all day at full speed with no pain at all. Surprisingly, the keyboard hardware itself doesn't seem to matter.
(Details: I mostly use a Mac, with caps lock mapped to control, NSRepeatCountBinding set to ^u, and -- obviously? -- I rarely touch the arrow keys.)
Wrist-bending to maintain the home row, I suspect. I have a different, self-taught style that partially involves holding my hands above the keyboard and using muscles all along my arms to move my hands without bending my wrists much - never had any problems.
Wrist discomfort with QWERTY completely disappeared upon switching to Dvorak.
I do always change one thing, and recommend it for others too, is to change caps-lock into a control.