Yes it will make a difference, the camera and
lens can work with each other or against. That doesn't make any sense. In any case both can have errors, sometimes you get lucky sometimes not.
Microadjust each
lens on each body. I find that my 24-105 is about +3 on both my bodies, but the 70-200 needs +10!! When I first got my 70-200 new it was terrible, needed something silly like +15 at 200mm and the opposite at 70mm. After sending it back to
Canon it came back still requiring +10 on my 7D but at least it was consistent through the range. Now I can confidently use it wide open.
Do a search here for microadjust, there are a few posts about it (I posted a couple of threads about my adventures!). It is easy to do with the 50D and you can't break it, it is just a setting that you can change back to 0 if you find it gets worse.