Plug-in hybrid electric vehicle (PHEV) technology may reduce fuel consumption and tailpipe emissions in many medium- and heavy-duty vehicle vocations, including school buses. The true magnitude of these reductions is best assessed by comparative testing over relevant drive cycles. The National Renewable Energy Laboratory (NREL) collected and analyzed real-world school bus drive cycle data, and selected similar standard drive cycles for testing on a chassis dynamometer. NREL tested a first-generation PHEV school bus equipped with a 6.4 L engine and an Enova PHEV drive system comprising a 25-kW/80 kW (continuous/peak) motor and a 370-volt lithium ion battery pack. For a baseline comparison, a Bluebird 7.2 L conventional school bus was also tested. Both vehicles were tested over three different drive cycles to capture a range of driving activity. Relative to the baseline school bus, the PHEV fuel savings in charge-depleting (CD) mode ranged from slightly more than 30% on the Urban Dynamometer Driving Schedule for Heavy Duty Vehicles and Rowan University Composite School Bus Cycle drive cycles to a little over 50% on the Orange County Bus cycle. However, the larger fuel savings lasted over a shorter driving distance, as the fully charged PHEV school bus would initially operate in CD mode for some distance, then in a transitional mode and finally in a charge-sustaining (CS) mode for continued driving. The test results indicate that a PHEV school bus can achieve significant fuel savings during CD operation relative to a conventional bus. In CS mode, the tested bus showed small fuel savings and somewhat higher nitrogen oxides (NOx) emissions than the baseline comparison bus. Further refinements to realize hybridization fuel savings in CS mode and calibrations focused on reducing NOx could lead to both higher fuel economy and lower NOx emissions in the next generation PHEV bus design.