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Best Handgun Defensive Caliber for Old Arthritic Granny?

A Ruger 10/22 YOUTH carbine
(extra slim stock, 16.1" bbl)
with an extended bolt charging handle
and loaded with a 30-round magazine
full of high velocity HP ammo

is probably the gun that would, in her hands, put the most rounds on target
in the shortest time, and unlike a handgun, a long gun can actually be pointed with a pretty good degree of accuracy.
Using the sights is not critical.
 
This is for home defense not for CCW.

I would say the needed criteria would be:
Low recoil
Decent round capacity
East to operate in regard to making ready to shoot and shooting. Not including cleaning and loading.
Terminal effectiveness
A small enough grip that a small weak hand could hold on to.

The calibers that come to mind are 22lr, 22wmr, 5.7, and 380.

Looking at some modern offerings, S&W make a high-capacity pistol in 22wmr and 5.7.
I am not in love with their terminal effectiveness and their grips are a little big for granny.
They do have great capacity and very low recoil.

Sig's P322 is a high capacity 22lr with an acceptable grip and low recoil.
But the terminal velocity is probably worse that the 22wmr and the 5.7. I am not sure how much worse in a 4-inch barrel.

Recently a larger size 380 has got my attention. It is a Beretta 80x Cheetah.
It has 13+1 capacity. Not too large of a grip. Larger than the modern-day pocket rockets so more controllable.
Low recoil. With some of the modern ammo by Underwood, it may be fairly effective.

What do you think?
Have you looked at the Keltec PMR30? My wife has a muscle disease and weak hands it may be the only weapon she can shoot. We have an E-Z in .380 she can’t shoot because of weight, recoil and hard for her to pull the trigger.
 
Perhaps, you are asking too much of granny. You've mentioned that she old, arthritic and weak. You've also mentioned 22lr, 22wmr, 5.7, and 380, none of which are my choice for home defense. Whether for home defense or CCW- as you know- one should be well acquainted with the firearm. One should be practiced and capable of using it with relative fluency. One must also be able to move quickly to the location of the firearm in the event of an emergency. Im concerned that these requirements make granny less likely to keep/use a firearm safely.
 
I've been through this before. It is what it is. That said S&W model 317. Light, 10 oz. Small, will fit her hand well and go anywhere. And has an 8rd capacity. With the 2" barrel, it'll have a loud report. Possibly ward off intruders. 22mag would be quite a bit more, probably too much.
 
I've been through this before. It is what it is. That said S&W model 317. Light, 10 oz. Small, will fit her hand well and go anywhere. And has an 8rd capacity. With the 2" barrel, it'll have a loud report. Possibly ward off intruders. 22mag would be quite a bit more, probably too much.
22 LR on top.
22 mag on bottom

Or a Shockwave in 20, or 410.
Those 410 round disks mixed with #4 would hurt
 

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