I've got a model 625 JM series. Given that the wheelgun isn't constrained by the same ammo issues that a .45 auto pistol has, I would like to know what type of .45 auto ammo would be good for a defensive application.

I like the idea of a keith-style slug, heavy (~255 grains or so) at a moderate velocity. I suppose ~ 800 ft/s would be nice with this sort of slug. Would such a load be effective and safe for the 625?

I do not reload. Can anyone recommend factory ammo that fits this profile? thanks in advance.

It would be hard to pick a bad .45 defense load, but your "ideal choice" is at least 20 years out of date, and a SWC is not the best profile for reloading a clip fed revolver. Any of the current JHP defense loads in a full-moon clip will load, eject, and reload easier, and are good to go on the terminal end.

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Science plus Art

Buffalo Bore's your huckleberry. 255gr 45APC +P

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So many S&W's, so few funds!!

Don't forget you're not restricted to 45 ACP ammo & moon-clips, if you don't want.

45 Auto Rim are also available from Buffalo Bore:

.45 Auto Rim (+P) Ammo - 255 gr. H.C. F.N. (1,000 fps/ M.E. 566 ft. lbs)

.45 Auto Rim +P Pistol & Handgun Ammunition

Speed loaders are available for the 45AR.

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I like Sierra's 240gr JHP for my (serious) 45AR handloads (I know you don't reload) but having a handful of 45ACP moon-clipped at the ready, just in case, is nice.

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Waiting for the break of day

I have that same gun and shoot auto rim exclusively.

Depending on what you are defending against, a heavy SWC can be a fine choice.

Edit: I have been using offerings from Magtech, specifically their First Defense ammo. Accuracy and expansion has been excellent for a "value priced jhp". I also use polymer and steel moon clips with 100% reliability.

SVT28

I have a 5" 625-2 and load mostly Starline 45 Auto Rim cases with a variety of plated and jacketed bullet types and weights mainly to keep my marksmanship acceptable.

I have a good supply of Federal Large Pistol Match primers that I'm using together with Red Dot and Bullseye powder

I don't use my 625-2 as a defensive weapon,I have a 686-4 and a Model 59 for that role.

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NEVER GIVE UP YOUR GUN