Is it safe to shoot squirrels with a .22?

Friend and I were just shooting them yesterday with a .22, had several instances where we couldn't shoot because there was no "backing" for the bullet. It's all part of hunter safety: know what's beyond your target.

My brother uses a .17
 
It is absolutely not safe to shoot squirrels with a .22. I had a friend in high school shoot one with a .22. The darn thing fell out of the tree and immediately went into full attack mode. Lucky one of the many backup shots from that old pump gun managed to stop the vicious little animal before it could do any damage. I would say it would be safe to use, at minimum, a .243 on squirrels. Anything less and you're taking your life in your hands.
A .22-.284 should do the trick, a 243 doesn’t have the velocity or knock down needed to safely dispatch one before it hits the ground.

 
I will not shoot them out of a tree unless the trunk is behind them with a 22. With a shotgun I certainly will.
 

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