A quote from famous author/shooter Ernest Hemingway on the effectiveness of the .22 round. Ernest's favorite platform was the Colt Woodsman:
"Now standing in one corner of a boxing ring with a .22 caliber Colt automatic pistol, shooting a bullet weighing only 40 grains and with a striking energy of 51 foot pounds at 25 feet from the muzzle, I will guarantee to kill either Gene Tunney or Joe Louis before they get to me from the opposite corner. This is the smallest caliber pistol cartridge made; but it is also one of the most accurate and easy to hit with, since the pistol has no recoil. I have killed many horses with it, cripples and bear baits, with a single shot, and what will kill a horse will kill a man.
Like the reference to RFK some posts back, not exactly a typical self defense scenario, is it? And with all due deference to Ernie and his confidence in his shooting ability, I believe he wouldn't be able to do it 100% of the time. Gene and Joe could move and they were hip enough to not just come straight on. I wonder if he could do it 50% of the time. Of course, all we can do is speculate. (I wouldn't bet against Jerry Miculek tho) And stationary targets at 'regulation' distances hardly constitute an equivalent scenario, either. As others have said, a .22 would be 'better than nothing'. But why settle for 'better than nothing' if the stakes are that high?