The most fuel-efficient Ford E-350 is the 2013 Ford E-350 Base which gets 12 MPG City and 16 MPG Highway.
It is important to remember factors such as driving style, weather conditions, and the use of features such as Eco mode can impact fuel efficiency. Fuel economy figures are based on EPA estimates for when vehicle sold as new. Fuel economy may vary for reasons like driving conditions and vehicle history. Unless specified, figures are for vehicles equipped with an automatic transmission. See fueleconomy.gov.