Hello SoulKiller,
Whenever you make any modification to a game it's highly recommended to backup the files you are modifying. If you are modifying a whole game then you can copy the whole program file for that game, located in the C: drive. You can copy this to another HDD or the current C: drive if you aren't worried about space. This isn't recommended though as it can lead to a corrupt game.
The better option to ensure that the game will work you can do a fresh install every time to switch between modded and unmodded.
Regards,
Ryan.