Originally Posted by revolvergeek

After looking at Gelatin results at brassfetcher.com, I would go with either the CCI Velocitors or Aguila SSS (assuming that they function reliably in your rifle of course). The Velocitors have a nice balance of expansion and penetration. The SSS penetrates deeply and yaws/tumbles once and should do a fair bit of damage. Reliability is the single most important factor though, and if you have any malfunctions with them then you need to try something else. If I was 100% betting my life on a 22 rim-fire I would likely invest in some very good Lapua / RWS / etc Biathlon or other competition ammo. You might pay $8-15 a box of 50, but it should be about the most reliable rim-fire ammo that you can buy.

Personally I don't see anything wrong with a 22 LR rifle used in a defensive role in a very limited set of circumstances (people with limited hand strength, need to limit penetration of missed shots as much as possible, etc). The big advantage is that you can afford to practice a lot with it and get good. There was a time when all that I had was an Iver Johnson TP22, and religiously shot a minimum of 500 rounds a week with it. You have to plan to make multiple neck and face shots, fast, under stress and in bad lighting 100% of the time.

That said, under normal circumstances a 22 would not be my first choice though. I would bet that if you crawl the pawn shops you can pick up an ugly used Mossberg / Revelation / New Haven 500/600 pump in 12 or 20 gauge for around $100-125.