Dan: I've had and recommended a number of the 21As in the 22lr and in each case they have been fine pistols that functioned each and every time. To my recollection I cannot recall even having a dud round in one of those pistols. However, a number of fellas have had bad luck with them and have referred to them as 'jam-omatics'.
When I got my first one, I just took it to the range with all its magazines (4 extras) and a paper bag full of left over 22 lr ammo - left over from every box I hadn't emptied in the past 10 years. They were of all mixed brands and flavors, high speed, target velocity, hollow points, truncated nose, solids, etc (if there's any other flavor), and shot the snot out of it until she started getting dirty and slowed down at about round # 350. I brushed out the chamber and banged out the last 150 rounds without a problem.
I started mine on a steady diet of Remington Hi speeds (the old golden bullet), and that load works all 5 of those pistols I am familiar with without problem. That is also what I carry in the pistol. When I go for a range session, I will empty the full mags into the target, then switch off to some easier loads - 40 gn CCI standard velocity or something of that flavor and play with it for a couple of hundred rounds. But, after finishing the range session, I will clean the piece and load everything back up with the Remingtons. That has worked for me for at least 1K rounds through that piece, and she keeps on tickin' without problem.
If you don't have much of a hassle switching handguns (buying one and if it doesn't work right for you taking it back for another) I would say try one of the 21As in 22lr first, and if you don't like it then go for one of the 25 autos. The centerfire may be more reliable for you. HTH. Mikey.