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The Greenhouse gases, Regulated Emissions, and Energy use in Transportation (GREET) model incorporated fuel economy and electricity use of alternative fuel/vehicle systems simulated by the Powertrain System Analysis Toolkit (PSAT) to conduct a well-to-wheels (WTW) analysis of energy use and greenhouse gas (GHG) emissions of plug-in hybrid electric vehicles (PHEVs). Based on PSAT simulations of the blended charge depleting (CD) operation, grid electricity accounted for a share of the vehicle’s total energy use ranging from 6% for PHEV 10 to 24% for PHEV 40 based on CD vehicle mile traveled (VMT) shares of 23% and 63%, respectively. Besides fuel economy of PHEVs and type of on-board fuel, the type of electricity generation mix impacted the WTW results of PHEVs, especially GHG emissions.