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Depends on why. The 6" S&W would be an amazing gun for tackling about anything on the planet. There is a large selection of bullet out there for it. The .50AE can not even compare for ballistics.

Well the DE is just a BA gun. Think of how many good movies it stared in. When Midway still had bulk bullets in .50 AE I was reloading for about $0.25/rd so very cost effective to shoot. I had wanted a DE for a long time but were out of the price range I was willing to pay. A couple years ago on here I found one, with accessories for a price I was willing to pay. It was such a good price I almost felt like I was stealing it.


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I would go S&W 500 mag in a 6-8 inch barrel. No offence to those that have the DE, but to be, its a bling weapon for king hood rat to keep the lesser hood rats in line.
 
I had a 5" S&W for a couple of years. If I was doing it all over again I'd do the same thing.
The 5" gun is heavy enough, but can be packed in a good holster without being in the way. The longer barrels don't lend themselves well to being carried, as I don't think the DE is a "packin" gun.
As far as ammo, fat chance on finding 50AE on the shelves, but the 500 S&W is fairly common on a well stocked shelf.
Power? There is no way the AE can touch what the S&W is capable of, plus the S&W has limitless choices of bullet style.
Not sure what you would pay for a DE in 50, but you can buy a brand new Smith for a shade over a grand.
Also, from what I learned shooting the 500 over a chrono, it didn't need a long barrel to get speed. 4" of rifled barrel did the trick. (5" guns have 1" of comp)
 
Too big and nasty, both of them . I realize that I am not MAN enough to handle either and that being said the wife would say that I am compensating if I came home with either.
 
The 50AE thinks its a bass *** and the 500 Smith knows it is...

I'd still rather have the 460 Smith in a wheel gun (I did for years) over the 500 but only if I needed it. I'd have a Desert Eagle in .44 mag over the .50 but that's just me.

Really with out your desired needs for cartridge it is really hard to give good advice.
 
I heard the .44 DE is super soft shooting and accurate.. but it's a brick x2!
I don't know if it's super reliable or not but those two things go far for a hunter/"plinker" gun.
 
For a handloader, I got to think the .500 has infinitely more possibilities. Without the concern of cycling a semi auto action, a fella could load anything from dribble out the barrel duck fart loads, to hammer of the gods magnum cannon barrages.
All that being said, .454 casull is as far as I've made it the big bore revolver ladder, so what the heck do I know.
 
I would pick the S&W 500, I didn't set out to be a revolver guy, but that's where I've ended up, I like bolt rifles and wheel guns. I especially like the big Smiths, as others have mentioned, having a variety of ammo you can feed them is pretty cool.
 

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