Like H&H said, penetetration. A Grizzly has skin 4 inches thick. I sold my 338 when I bought a beautiful 375. A 300 is not recommended by outfitters for dangerous game in Alaska, though many are killed with it. A 338 is the minimum that most outfitters recommend. The 300 is recommended by a few gunwriters. I feel sure that I will never go to Africa, so, the 375 will flatten anything that I will ever get to hunt on this continent. Good luck with your choice, but remember, you can get an extremely versatile caliber that has true power with the 375. I also noticed that the 338 handloading market is not nearly as varied as the 375. I can get anything from 210 grains to 350 grains easily.