Yes, I believe it does make a difference. My husband plays 6 and 12 string guitar. I play bass guitar. When we look for a guitar for my husband, it is nothing for me to wait all day for him to find one that fits. The last time he walked into a music store, he made a comment of not liking the looks of a brite red strat....he played every guitar in the house and could not find one he liked. He finally asked me to get him the red strat....after 3 strums, he said, this is the one...it fits....had i known, i would have made him play that one first rather than wait hours for him to play every guitar in the store.
I have found there are some guitars that practically play themselves where others are uncomfortable to the hand and are not a joy to play. Once you find a guitar that fits both your music style of playing as well as your hands, hang on to it because you may never find one like that again.