Proton exchange membrane fuel cell (PEMFC) technology for use in fuel cell vehicles and other applications has been intensively developed in recent decades. Besides the fuel cell stack, air and fuel control and thermal and water management are major challenges in the development of the fuel cell for vehicle applications. The air supply system can have a major impact on overall system efficiency. In this paper a fuel cell system model for optimizing system operating conditions was developed which includes the transient dynamics of the air system with varying back pressure. Compared to the conventional fixed back pressure operation, the optimal operation discussed in this paper can achieve higher system efficiency over the full load range. Finally, the model is applied as part of a dynamic forward-looking vehicle model of a load-following direct hydrogen fuel cell vehicle to explore the energy economy optimization potential of fuel cell vehicles.