Settle in folks, this is going to be long. Since the overwhelming majority of posts on the TDR claim that this or that mod will improve mpg, I want to share an alternate viewpoint with the "new" folks. I don't feel that "I'm right, the other guys are wrong", I just want the new guys to take their time, do their own research, and read all the old posts before deciding what mods are right for them based on just one or two threads.
With my 6 speed HO, the only mod that I have done that had a measurable, consistent impact on mpg was adding 275 RV injectors (maybe ~0. 5 mpg?). (I really like the 275's by the way - a little more power, no smoke unless I really put my foot into it, and just a hint of mpg improvement. ) Both the VA and EZ boxes hint or outright claim improvements in mpg; I did not see one in "controlled" trips - 110 mile commute to work, mostly open freeway, setting cruise control and checking for several thousand miles of data back and forth over the same road. Every time I thought there was a difference, it was easy to explain away by looking more closely at my notes and data. Headwinds, tailwinds, outside temperature, other weather factors, tank-to-tank fill up variations (which show higher or lower numbers than expected on the next fill-up) always made more difference than hooking or unhooking a box. It is possible that the experience of ETC's and autos may be different; since extra power has secondary effects like changing transmission shift points. It is also possible that others got a truck that wasn't "tuned" right from the factory and then "fixed" their problems with add-ons. My answer applies to 6 speed HO's, 24 valve engines, and may be very wrong for 12 valve engines or even other variations of the 24 valve engine.
But I also believe that some (please note, I said "some", not "all") of the folks who report big mpg gains with this or that add-on probably made several runs enjoying the increased power, then made one or more runs driving very carefully to check mpg. I also believe it might have been the careful driving that caused them to get really great mpg when they kept their foot out of it.
Again, returning to my experience, before mods, I could get over 20 mpg driving carefully and slowly (<65 mph). After numerous mods, I still get over 20 mpg driving carefully and slowly (on summer fuel). I can slow down even more and consistently get over 21 mpg. Throw in some around town trips, and it's more like 18 to 19+. Throw in a lot of around town trips, or take a long trip where I drive faster on the freeway, and it can drop under 17. If I drove like some of my friends, I'm sure it would be under 16. I also think I could get another 2 mpg if I removed my camper shell with racks, and went back to street tires vs. my 295 BFG AT's, but then it wouldn't be the same truck if I did those things.
Money spent on mods should be spent for fun, or because you want power, or for exhaust brakes and Espar/Webasto heaters, or winches, or whatever tickles your fancy. Money spent on mpg will generally not provide economic payback.
Nobody wants to hear this, but if you want better mpg, think twice about mods that cost mpg like big bumpers, light bars, ladder racks, brush guards, big aggressive tires, etc. , and only get the ones that are really important to you. Then slow down, even if you only slow down 2 to 5 mph it makes a difference on these big trucks.
(soapbox returning to storage location now - breathing deeply... )