I have the 357 sig full size, and the 45 midsize. I carry the 45 for ccw, and my 357 stays in the case untill it's range time. the 357 is by far my favorite caliber...it has very impressive ballistics. I have had zero problems with either. I've done several penetration test with both, and the 357 simply out performed the 45 as far as power and penetration. As far as human targets in a "self defense" situation, I'm a little more comfortable with the 45, and I think anyone, or anything behind the target would be alot safer. The 357 would probably keep going, and going.........