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I worked at St. John Main hospital's Emergency Room for 2 years in Detroit, and we got shooting victims nearly every night, sometimes multiple victims.
I can say that .22 rounds are EXTREMELY DANGEROUS, and from a medical perspective, I can tell you why.
Their ability to under penetrate. What is this, you might be asking? Case in point, 2 real life scenarios that happened:
.22LR to the eye.
Bullet did not travel through the skull like a normal caliber. It entered the skull, entered the brain, and ricocheted off the back of the skull, re-entering the brain on another separate path, in which it ricocheted at least two to three more times, causing this man's brain to turn into giant swiss cheese.
He was dead on arrival.
Second case:
22LR to the upper chest. Ricocheted off the right clavicle, went diagonally down, through the heart and lower left lung, part of the liver, and exited near the top of the left buttock.
This man was treated in the ER from the OTHER gunshots he received (we did not even notice the .22 bullet hole because it was so small) and came to us alive. He died in surgery, from the .22LR.
That being said:
A .22LR is MUCH more effective than your fist, and/or a legal sized pocket knife. Would I choose it as a primary self defense caliber? Probably not, however, if it was the only recoil that my wife-to-be could only handle and she were to get her CPL, I would rather her have that than nothing at all. Ultimately, we've all agreed at one point in time that shot placement is key, not caliber size. Though in the majority of situations you will probably not be thinking about shot placement as much, I do know from personal experience that they can be effective.
Also, I know this was mentioned before, but check out the .22 Magnum if you're set on .22; especially the Charter Arms Pathfinder. It's a SWEET little revolver, comfortable, and cheap to shoot. A good buddy of mine has one, and I love shooting that little cannon. Not to mention it's small enough to fit in your pocket, and costs around $250.