I used a .223 with a 55 gr. v-max tip to drop my 3.5 year old mulie this season, actually I used 3 but he still went less than 5 yards between the first and 3rd shots It was a bolt action too. 185 Yards. Mulies are dumb during the rut.I could have dropped him with a 22.He was so busy trying to ride a doehe had no idea what hit him. My deers lungs were pudding.When a whitetail hears a gun it takes off, evenwhen it is hit. A muley hears a gun shot and it puzzles them, so they dont bolt immediately.

My go to gun for mulies is my 7mm Rem Mag.

.270 or 7mm. mag.

7mm STW. Good luck.

This year I used my new Remington model 700xcr in 270wsm. Using factory Winchester 150gr. Winchester Power Point ammo. Shot was a lasered 298yds. Only took one shot and took out both lungs.
http://i248.photobucket.com/albums/gg178/700xcr/1209070959-00-01.jpg
http://i248.photobucket.com/albums/gg178/700xcr/1209071000-00.jpg
http://i248.photobucket.com/albums/gg178/700xcr/1209071041-00.jpg
http://i248.photobucket.com/albums/gg178/700xcr/1209071510-00.jpg

The 7mm-08 or the 308 either one will handle mule deer or elk

Whenever I head out west for mulies and/or antelope, the first rifle that goes into the case is my .270. Next is either the '06 or 7-08 as a back up. But the 270 was all I ever needed. Now to answer your question, if I were to pick a mulie cartridge today it would be #1 the 270, #2 the 7mm RM and never look back. There are a lot more options out there that would perform equally as well but these would be my choices.

As Jeff Ovington stated muleys are not hard to kill. Seems about half the whitetail I've seen shot ran a ways after the shot. I've yet to see a muley go more than 10yds after the shot. 95% of those where DRT. I think people think too much into cartridge selection. I've used my .243, 25-06, 7RM, and 30-06 and noticed Zero difference. I mainly shoot the 25 and the 7 just because the flatter trajectory helps with the longer shots out here. Brett

IMHO-someone saying the 270 isn't enough gun for mule deer is laughable!!!

Here we go again. Think open country, flatter shooting.. but its still just a deer so use a good bonded bullet and know your limits.. You certainly don't need a mag, especially if you don't want to waste meat.

I use a .308 as my regular hunting rifle when hunting muleys. A .270 will do the trick just fine though.