"The most effective .22 lr load is the same load that started the trend to high velocity hollowpoints decades ago: the CCI 32 grain Stinger. The 32 gr Stinger is advertised at 1,500fps from a rifle, but it still reaches 1,255fps from a handgun. Surprisingly, it does not expand at these velocities. Instead, it tumbles base-over-nose to a depth of 9.8" in ballistics gelatin. The average adult male torso is 9.4" thick front to back. The Stinger produces enough penetration for the frontal upper torso shot. The other "hyper velocity" rimfires like the Remington 33 grain Yellow Jacket perform in ordinance gel just like the CCI 32 gr. Stinger. For years ammo experts have been saying the .22lr does not have enough power to stop hostilities instantly. Now we know the best 22 rimfire load is successful just one time out of three attempts. Based on 395 shootings, the Stinger has a 34% one-shot stop.
Second place in the 22 lr caliber are the 36 to 37gr. lead hollowpoints. In actual shootings, these "high velocity" lead hollowpoints are just 29% effective. The original 40 gr. roundnose lead has the dubious honor of being the least effective of the known defensive handgun loads. This classic RNL plinker is just 21% effective with one torso shot".