What I have found is it all depends on your fender. There seems to be a lot of variance in the fender to tire clearance from the factory. I hogged out my rear fender holes and still couldn't get 1/4" clearance. I ended up welding in a set of Native Customs brackets. I firmly my situation was rare and you should be good to go with a 3/8" bit and holding it up as you tighten it down. I've helped a couple of other guys out mounting their 21" and have not run into my problem with their bikes. One fit with no need to enlarge the holes. The tolerance is all over the map.

Hope you like your new 21"

Zach