Yes and no. I have never had a problem, and if they do happen they are few and far between. Since when you change a tune you are essentially rewriting the computer, there can be data transfer issues, and if your battery doesn't have enough power it can also cause some major problems. I know Jack always hooks his truck up to a charger whenever he changes tunes just to make sure there is always enough power getting to the Gryphon and the ECM.
So yes, do not change a tune when you are far from home or a towing company (yes a mistake can make the truck not run), but problems like this won't happen most of the time. Like I said, I have had 2 trucks with multiple tune changes on each and I have never seen anything go wrong, and I wasn't hooked up to a battery tender or charger either.
