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So I got to thinking; once a person is hit with a bullet whither it be 22 or 500 mag, they are most likely not going to keep walking your way like they are the terminator or something....
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Caliber doesn't matter as much as having a gun, any gun when you need it.
Now, consider what you said, and how you said it. Someone walking at you (with clear intent to do injury or murder) is only one possible situation.
Another possible situation is several someones advancing and threatening you. There are almost as many possible situations as there are things and people in our lives.
If small calibers didn't
ever work, we wouldn't have them.
Everything above mousegun increases your odds a bit, until you reach the point of having too much cannon to manage.
If the situation gets to having to use the gun, then the one you can make the most effective is best. And that is a combination of bullet performance, gun performance, and your performance.
Caliber matters, but only hits count.
(note sig line....)