Info straight from Ford...
From what we have learned from the techs at Dearborn, fuel mileage is directly proportional with gear ratio.
For instance, I have a 450 4x4 DRW w/ 4.88 gears and am getting approx 9.8 to 10.2 MPG. This is as good as it will get for me at the moment with only 13,000 miles on the odo. As the engine breaks in the fuel mileage will creep up a little more. When hauling -- 19,000 to 20,000lbs -- we tend to get 8.6 to 8.9 MPG. Keep in mind our neck of the woods has a lot of hills at 4% to 6% grade. On straight flat highway driving and a full load we tend to get around 9.3 mpg.
A 250 4X2 SRW w/ 3.73 gears will get great fuel mileage compared to my truck. Close to 19 or 20 depending on driving style.
For those of you with the 4.88 gears you may want to change your driving style. From what we learned if you keep your RPMs under 2k then you will see improved fuel economy. The turbos on our engine draw a lot of fuel if you stand on it from a dead stop. If you ease into the gas and build power moderately under 2000rpm you will keep the turbo from kicking in too hard. Even when you drive conservatively like this you are still faster off the line than a stock 2001 7.3 diesel F-250.
In this time of expensive diesel prices driving a little slower off the line far outweighs a huge and painful fuel bill. Up here in the Northwest $4.75 to $4.60 a gallon is pretty common.