If you consider a buffalo serious hunting, then yes. I've killed buffalo with all the '76 calibers, except the .40-60. The .45-60 didn't do very well, but both the .45-75 and the .50 Express worked very well. Shot placement is always the key. I've shot two with the .50 and several others with the .45-75. All of the guns were original Winchesters. The new reproductions may shoot differently because of the rifling twist. The original .50-95 has a 1 in 60" twist. I've found that the factory 300 grain bullet will not stabilize until it is out about 60 yards from the muzzle. I've also found that the maximum killing range is about 250 yards. Both of the buffalo I shot with this caliber in a rifle were out about 85 yards. On the other hand, the .45-75 performed flawlessly. The original twist is 1 in 20", which makes the heavy 350 grain bullet stabilize right out of the muzzle. As far as I'm concerned, the .45-75 is the ultimate caliber in the '76. I've made one-kill shots with both rifles and carbines in this caliber at distances out to 124 yards. No matter how you look at it, these guns are as much fun to shoot as anything I've ever owned.
Adios,
Buck