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It depends. Depends upon the motor, the weight of the truck, the tire size, and the speed you drive. In general less rpm equaly less fuel, but if the motor struggles to maintain speed, downshifts frequently on grades and into headwinds, then milage will suffer. The key to milage is to keep the vehicle moving as fast as possible with the least amount of throttle input, and the combination to achieve that is different for each motor/truck combo. A 4.9 2wd F150 will need different gearing than a 5.0 4x4 F250.
If your truck is a stock inline 4.9 6 cylinder then the 3.08 gears should be fine. If it is a 5.0 V8 like mine then the 3.08s suck. I have 3.55 in mine now. The 4.9 makes its power in the lower rpms whereas the 5.0 doesn't make much power in the low rpms.
Best mileage is not achieved going "as fast as possible" with low engine speed, but going about 45 mph with low engine speed. Above that, wind drag (which increases with the square of speed) starts to play a major role. Most vehicles will get their best mileage at around 40-45 mph, as this is about the lowest speed they can hold top gear on level ground, plus the aforementioned drag factor. The reason many people don't ever see this mileage is that there are few places in this country where you will drive 40-45 mph without also being in stop-and-go traffic for extended periods. If you did run through a full tank of gas at 40-45 mph without stopping, you will never surpass that mileage in your vehicle, all else being equal.
One more thing. I think you'll find that the F150s that get the best mileage are the ones with the 300 engine and a 2.73 or 3.08 rear ratio and a 5-spd between them. The 300 has the low-RPM torque to overcome the poor gearing, then the high ratio (low numerically) gives good mileage at speed. You just can't tow much or get anywhere quickly.
My 351/E4OD/4.10 is clear at the opposite end of that scale...
Best mileage is not achieved going "as fast as possible" with low engine speed, but going about 45 mph with low engine speed. Above that, wind drag (which increases with the square of speed) starts to play a major role. Most vehicles will get their best mileage at around 40-45 mph, as this is about the lowest speed they can hold top gear on level ground, plus the aforementioned drag factor.
You mis quoted me, I didn't say "with low engine speed", I said "with the least amount of throttle input". The result is we essentially said the same thing in different ways and are in agreement.