Battery degradation strongly depends on temperature, and many plug-in electric vehicle applications employ thermal management strategies to extend battery life. The effectiveness of thermal management depends on the design of the thermal management system as well as the battery chemistry, cell and pack design, vehicle system characteristics, and operating conditions. We model a plug-in hybrid electric vehicle with an air-cooled battery pack composed of cylindrical LiFePO4/graphite cells and simulate the effect of thermal management, driving conditions, regional climate, and vehicle system design on battery life. We estimate that in the absence of thermal management, aggressive driving can cut battery life by two thirds; a blended gas/electric-operation control strategy can quadruple battery life relative to an all-electric control strategy; larger battery packs can extend life by an order of magnitude relative to small packs used for all-electric operation; and batteries last 73–94% longer in mild-weather San Francisco than in hot Phoenix. Air cooling can increase battery life by a factor of 1.5–6, depending on regional climate and driving patterns. End of life criteria has a substantial effect on battery life estimates.