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I suggest you read the owner's manual. There are some specific recommendations from Ford. You can just gas and go, but I think Ford recommends running normal gas occasionally. Generally speaking, E85 will net you more power but lower gas mileage.
It does offer some pre ignition protection but if your vehicle is running right this isn't an issue. You'll pay less per fill up but fill up more often. Using e85 will take about 25% more fuel per mile.
I'm glad we don't have E-85 in my area, I've been running ethanol free in mine, I know it's prolly a waste of money as the truck is a "Flex Fuel" vehicle, (just hard headed, I guess)!