The MOST comfortable way I have found to carry is OWB, with a good belt, and skip the belt loop at 3:00.
Like everyone else, I have tried damnnear everything, Cross breeds, Milt Sparks etc. etc. I have tried appendickectomy carry, and just don't care for it.
I'm sure I will get flamed for this by the holster snobs, but I love a Galco Concealable Belt Holster, again skip the loop at 3:00 and you can slide the gun forward for max concealment, slide it aft when you jump in the truck and it's very comfortable.
I'm roughly the size of an NFL Linebacker (retired lol) at about 260ish, and I carried a Sig 229 like this for years with no issues. Obviously, you have to be able to dress untucked.
I also have the Miami Classic II for my Sigs, 1911's and bigger Wheel guns, and they are cool when you can conceal them, this is the most comfortable way to carry a larger handgun, for me.
My EDC is a 365 in a Versa Max and it is comfortable enough and it works