Difference in what: long term hand health, comfort, efficiency?

Anecdotally, I taught myself Dvorak for a couple of months. I never reached speed parity, but typing felt significantly better. The number of common words which roll off of the home row was a treat. I could easily believe that this would put less pressure on keyboards than QWERTY.

My ultimate blocker was keyboard shortcuts. You get into a weird spot if you choose to maintain the original character chord (DVORAK CTRL-C would be CTRL-I on QWERTY) or force the QWERTY layout character.