The dealer stresses the main thing to keep up with on this engine is oil and air filters. If you neglect the oil, you put the turbo and injectors at risk as they are oil cooled. If you neglect the air filter, dirt can bypass it, 'sandblast' the turbo blades, which fail and chunk metal bits into the engine, causing cylinder wall and ring damage.
Other than that, since I pull a trailer, I change the transmission fluid per Ford's recommendation (the auto trans holds up better than the manual - Ford dropped the manual in 2004 I think).
I am sitting at 255k+ miles now...no problems and still running very strong; no smoke, doesn't burn oil, etc. The dealer I use has multiple customers with 500k+ miles on this version of the super duty.
“Other than that, since I pull a trailer, I change the transmission fluid per Ford’s recommendation (the auto trans holds up better than the manual - Ford dropped the manual in 2004 I think).”
My dad bought his F250 new in 2004, and the manual transmission was still available then. He went for the automatic in his.
And amazingly, he’s had no problems with the 6.0L Powerstroke in his truck. The guys who put his engine together must have really been on their game that day!