No- as long as you have it set up properly. You always have to set up your guitar if you change your gauge- it doesnt matter even if you're going from regular to hybrids. My friend even finds that he had to get his guitar set when he's switiching from a different brand, even though he's using the same gauge. I used to do experiments on my strat. Since I like to do a lot of bending when I play lead and I like to pick and play the bass at the same time while playing rhythm, I wanted to get the best of both worlds so I experimented by putting very thick strings on the bass and 9's on the treble strings. It sounded terrible at first so I have to have it set up so that the neck could properly accomodate the different string tensions. After the set up, the buzzing and the sharpness of some of some of the notes disappeared.