Bison

What cut of roast? How thick/weight? I would smoke it to medium rare with a liberal (mostly salt & pepper) brisket rub then rest it and reverse sear it for some color. Cut thin against the grain. I used to get bison back home in PA (there was a bison ranch a couple of miles from me) but haven't cooked it in a long time. I'm looking forward to seeing what you do with it.
 
Whatever you have will be analogous to a cow pretty much, just MUCH leaner. How much it weighs or how thick it is doesn't matter. You wouldn't cook a chuck roast the same way you would a sirloin tip, for example.
 
So assuming it is "pot roast" and not a prime rib or tri-tip... I still would do it as I mentioned. If you don't like medium rare, of course medium is an option (any more done than that and you might as well do it in the slow cooker :p) In all seriousness, you might want to smoke it for flavor and then slow cook it with some vegetables and liquid until fall apart fork tender.
 
My father in law raises buffalo and eat buffalo quite often. Slow n low is perfect for buffalo meat as it is quite lean in fat content.
 
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