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Ben, I would always choose a center fire round over a rim fire round. If you want a 380 revolver fine, but I would just get my wife a nice 38 special chambered revolver. Like one of these:--https://www.budsgunshop.com/catalog/product_info.php/products_id/26498/s%26w+m642+38+special+stainless------------https://www.budsgunshop.com/catalog/product_info.php/products_id/70712/s%26w+m442+5rd+38sp+%2bp+187%22+no+internal+lock

Ben, 380 will will the vote here Sir. 380 will be more effective up close and personal. Just take your wife to the range of if you have the land to get her comfortable with firing it. I recommend : https://www.budsgunshop.com/catalog/product_info.php/products_id/56780/hornady+380+auto+critical+defense+90+grain+critical+defense

No doubt about it the .380 is better than the 22Mag

Ben - Certainly the .380 is superior to the 22 mag for self defense. But the "best" for your wife is whatever she feels more comfortable with. Let her try both a revolver and one or two of the excellent .380 semi-autos on the market. Check the Springfield 380 EZ model, especially. If she is more comfortable with a small semi auto pistol, then she will actually carry it. If she has a revolver that she doesn't particularly like, just because you or someone else think that's what she SHOULD use ... then she won;t carry it and you;ve defeated the whole purpose of arming her. Give her a chance to choose - and let her decide, after trying a few for herself. Let her soot a 9mm pistol even - like a S&W shield. These gals are much smarter than many give them credit for .. and she will carry something she likes ... which is , I assume, the reason you are buying her a firearm - self-defense.