Mule deer often live in big wide open areas, so I prefer a flat shooting caliber that I can shoot accurately out to 450 yards. Some can shoot farther, but that is about the end of my comfort zone for good shot placement. I use a 300 win mag with 150 grain hornady interbonds. The 300 win may be overkill for some, but I am usually elk hunting at the same time I am after Mulies. The main thing is to have a rifle you shoot well, and have practiced with in real world conditions, since shot placement is the most important part of the equation.