I had an 18 f150 5.0 4x4 with a 3.31 rear end, crew cab 6.5' box. From 5,000 to 13,000 miles it averaged 20.2, with about 2,700 of the miles coming from a trip to Maine and back. On that trip, running about 75 mph average, I got 22.4 on the way out and the overall trip was 21.4. I was amazed. After that, once home, the remaining miles brought me down to 20.2. On the road with those 3.31's it just f'ing cruised. It went back at 13,000 miles under a lemon law buy back for transmission issues that started back at 600 miles and they just couldn't get it right. I'd say 18.5 is doable as most of my miles are from 5 to 20 mile trips.
I replaced it with an 18 3.5 ecoboost 4x4 (couldn't find a 5.0 due to year end and got a screaming deal on a loaded 3.5 Lariat). 3.55 rear end, crew cab, 5.5' box. I have just under 5,000 mils on it so far and the average is 18.3 since day 1. I just got back from a 600 mile trip to Duluth and running 77 mph I got 18.4. This is with the winter blend of gas. Always seem to get better mileage with the summer blend here. I'll reset it at 5,000 and see what the next miles bring, but that 3.55 will not get the mpg that the 3.31 had as at 77 mph it runs about 400-500 rpm's higher. I don't remember exactly that the 5.0 with 3.31's was running for rpm's at 77 mph but I think it was around 1,500. Maybe someone can weigh in on that.
The 5.0 with the 3.31 seemed a bit doggy to me, but I'm pretty sure the 3.55 would fix that.