A prediction-based power management strategy is proposed for fuel cell/battery plug-in hybrid vehicles with the goal of improving overall system operating efficiency. The main feature of the proposed strategy is that, if the total amount of energy required to complete a particular drive cycle can be reliably predicted, then the energy stored in the onboard electrical storage system can be depleted in an optimal manner that permits the fuel cell to operate in its most efficient regime. The strategy has been implemented in a vehicle power-train simulator called LFM which was developed in MATLAB/SIMULINK software and its effectiveness was evaluated by comparing it with a conventional control strategy. The proposed strategy is shown to provide significant improvement in average fuel cell system efficiency while reducing hydrogen consumption. It has been demonstrated with the LFM simulation that the prediction-based power management strategy can maintain a stable power request to the fuel cell thereby improving fuel cell durability, and that the battery is depleted to the desired state-of-charge at the end of the drive cycle. A sensitivity analysis has also been conducted to study the effects of inaccurate predictions of the remaining portion of the drive cycle on hydrogen consumption and the final battery state-of-charge. Finally, the advantages of the proposed control strategy over the conventional strategy have been validated through implementation in the University of Delaware's fuel cell hybrid bus with operational data acquired from onboard sensors.