Hey, I own 4 Muzzleloaders, 2 .50 cal's and 2 .45 cal's. For taking Whitetail Deer, both do their job. I think the biggest difference is in Bullet Selection. Next time you are in your local Sporting Goods store, check out the selection of bullets, you will find that .50 cal will be 75% of the total. Also, most manufactures make more models in .50 cal then .45. One man's opinion.