Looks as if you have a pretty good selection of women friendly guns for your wife already, unless your wife just doesn't like any of them for one reason or another. My wife has a Ruger SP101 357mag and a 12 ga Mossberg Persuarder for the house, deadly with both! Start your wife off with that 22, let her get used to it and work up from there.

My wife never liked guns . I took her to the range one day and put a round in my Sigma and talked her into a go with it . Bang. Turned around and handed it to me and that was all she would shoot it . Did not like it . A few monthe later I was in drooling at the gun shop and had my wife along told her to pick one out she liked for her birthday. Well she ended up talking to a salesman who was a retired fed. . I came back after a while and she picked out a Ruger LCP 380 . She had a little 22 in mind until her little visit . Pretty snappy but I did not say anything . Happy birthday And signed her up for a CC class .
Home to the range .Bang . to much recoil and noise . Ok I said why did you get this gun . She gave me her reasons . I told her then go with that .End of that session . Bought her a lazer Just a point and shoot anyway . Ohh she liked that . Pretty sexy. Off to the range told her load it up and blast away . Just shoot do not worry about hitting anything today . Then we shot the 22 . She now likes the 380 no big deal . She now took the cc class .Had a great time and changed her attitude . She carries the 380 and goes to the range whenever I go . Now I will slowly move her into bigger guns .

+1 except if she is recoil sensitive, I would go with a 20. If it is too big, you can get a youth model that is scaled down.

pink grips help women get excited bout guns. 22 mag is good choice or steel frame 9mm like a makarov and very cheep iffin she dont like it lol

I was actually thinking one of those 30-shot .22 magnum autos by Kel-Tec or an older Grendel.

Well... it did not go too well. She shot the .22 LR once and would not shoot it again, much less anything else. She is very brittle and just does not like guns. All I can do is pray nothing ever happens that she will need a gun.

Just last weekend I was teaching a lady friend of mine to shoot. Never fired a gun before in her life.
Started her out on a Model 18 4" .22 to teach the fundamentals.
Switched over to a 4" HB Model 10. Began with light wadcutters, then standard velocity lead and finally to +Ps.
She caught on quickly, did pretty good for her first time, but most of all she had fun doing it. The woman was giggling her head off when she made a good hit. She's already asked when we can go again.
I let her take the Model 10 home with her.

My wife has her own revolvers that she carries. However, here on the ranch, for home defense, we have my old S&W Model 28 in our bedroom at all times.

We also have two 22 ga shotguns, one in the house and one in one of our barns. My wife can outshoot me with the shotguns.

Sorry about that. Please correct that to 12 ga shotguns.

I suggest starting out with a .22 caliber revolver it has very little recoil and very little blast. Then once she mastered the .22 upgrade to a larger caliber revolver.

The SP 101 has the weight that is needed to help with recoil.I'd suggest getting her up to speed with it,since you already have it,starting with milder loads,working on DA trigger control,and move up gradually to a good performing short barrel load.
The first thing a gun shop employee wants to show a female is an airweight J frame. Wrong move for a novice. Even I would choose an SP101 over any J frame.
These guns are thoroughly vetted,and have been in production for a long time. No problems.

If she is timid with the gun it is importamt to be patient with her.Explain calmly that the gun will not hurt her and try to get her to understand that it is an inanimate object that cannot control her,but she can control it.
Try to convince her(calmly) that with time and practice it will become easier and even fun as she inproves.

__________________
Blessed be the Lord,my Rock

My wife was married to her CZ75B - until a few weeks ago when I happened across a very nice condition 586-1 with a 4" barrel (along with a few other guns, what a great week it was). She promptly declared, "Mine!", and it's been hers since. It's such a beautiful gun too with that blueing, it reminds me of a Python. The embarrassing part is she's already a better shot than me with it. I blame it on my being 10 years older, with 52 year old eyes. That's my story, and I'm sticking to it. However...

All that being said, our shotgun is the goto gun for home-defense. If I'm not home, she can handle the shotgun fine by herself. If I am there, then she can back me up with a handgun.

Some time at the range with your wife shooting the bedside shotgun is a better recipe for home defense than any pistol can ever provide. You can't CCW a shotgun (well, I can't, and she can't) so a pistol must suffice for around town, but at home the clear choice is the shotgun, the king of home defense weapons.

Lot's of good solid opinions expressed here. I urge you to get a wheel gun. Pick it up, point it and shoot. This will be panic time for her in home self protection, and she will not have time to think about a whole lot of things if she has a auto. Is there one under the hammer? Is the mag seeded properly, is the safety on or off. Don't burden her with these decisions. A handgun that "FITS" her hand is most important and a smaller wheel gun is the way to go. If recoil is a problem for her, go with a 9mm. Stay away from .380. If she has to shoot someone, go with this "A dead man cannot testify against you/her in court".