I have tried .50 explosive rounds, Gauss rifle, Elijah's advanced LAER, satchel charges, and everything that comes in the add-on with no luck. How do you kill these guys? Normal marked men are bad enough these guys are way tougher. (Deathclaws are easy with the advanced weapons. ) I am at level 45+ character playing on hard mode.

irradiated marked men gain strength and substantial health regeneration from radiation. brilliant statement, i know. typically (if not always) there is a warhead or radiation source nearby. you have to destroy the warhead or lure them out of the irradiated area. or else you have to hit them with some serious firepower.

i usually go with brush gun (medicine stick if possible) with some hand load rounds. it will do more damage than the anti material rifle with stock rounds and brush gun/medicine stick have a higher rate of fire. have you tried stealth attacks? i've also had good success with the riot shotgun and slugs. it will take a whole magazine, maybe two, but they will go down. vats headshots are effective especially with a high critical build. i haven't tried the avenger mini gun, but seeing as how it will destroy just about everything, i would think irradiated marked men wouldn't be too different. 45 submachine gun with hand load is rather formidable as well. as is the light machine gun (with hand load of course).

my typical LR loadout is: medicine stick with hand load rounds, riot shotty with slugs, light shining in darkness with hand load, AMR with hand load.

reading your level and weapons of choice, i'm surprised they are not dropping. my guess is they are regenerating health too quickly.

i only play on hard/hardcoe.

I found that they lasted about a second on my Minigun playthrough, thanks to Avenger. That said, you need a weapon with high DPS & AP rounds more than you need a weapon with high single shot damage. You also cannot afford to let a Marked Man(Or Irradiated NCR Trooper, or Irradiated Legionnaire) go after damaging them. They'll just regenerate. You have to keep the pressure on a single target until he dies.

-Nukeknockout

That's not entirely true. As long as the single shot weapon deals overwhelming damage then its fine.

I used Paciencia with Hollow Point rounds with my critical hit build on very hard. Most of the time its a one-shot to the head with irradiated marked men. No sneak attacks needed.

On a high crit build you can use high powered single shot weapons and score critical hits to kill them.

If you don't have a high critical chance then I would suggest going with weapons that have a high rate of fire.

Thank you for helping. I guess I will try the .45 machine gun and the Avenger. Hope the Deathclaws will stay away.

I used the silenced COS rifle with AP rounds. Stealth mode with a Stealth Boy and a head-shot from behind. Works every time! Two quick head shots to a Deathclaw works too.

I use Annabelle and my strongest weapon for my style. The Red Glare works well. If it's big, explosive and instant as you can get, use it.
Nothing subtle about it, you can't afford to be. Get to high ground if possible, get their attention in as small a groups as you can and blast away. Run to a none radioactive part, if there is one, that they and the irradiated deathclaws can't get to.
And blast away till they are dead. Avoid close contact fighting if possible. It's laggy as f**k.
And don't use vats because it crashes the game and the machine or you die messily with it glitching all over the place.

Stealth and sneaking are a complete waste of time and energy. You need brute force and a high vantage point that is marked man and deathclaw proof.

In Old World Blues I would agree with you, but I've beaten Lonesome Road with Sneak/Sniper character. It was very satisfying.

If you have the balls, the collapsed highway where the nuke hit is a perfect spot for that, but you'd need Rad-X

A Light Shining in Darkness worked for me.

My load out consists of the following assault carbine.with all ammo types 10mm, guass rifle(max charge ammo which is also usefull for ridding annoying legion assasins) Sniper rifle (with all ammo types and supressor) katana
Armour us army combat armour sunglasses (coz they are cool) and 1st recon beret n rebreather if needed, chems all kinds..
E-DE should make em appear before hand so you can get.sneak crits

Well, you can take the overkill route: Gun + Mini-Nuke = 0 problems.

Hmm, myself I would go with SPRTEL wood, or a minigun. Those two guns annihilate MMs all day long. As for deathclaws, a riot shotgun backed with the Shotgun Surgeon and Stay Back perks completely neuter any threat from those overgrown hellbags.

And yes, as has been said Red Glare is a good choice from range.