A heavy-duty vehicle (HDV) module of the Greenhouse gases, Regulated Emissions, and Energy use in Transportation (GREETTM) model has been developed at Argonne National Laboratory. The fuel-cycle GREET model has been published extensively and contains data on fuel-cycles and vehicle operation of light-duty vehicles. The addition of the HDV module to the GREET model allows for well-to-wheel (WTW) analyses of heavy-duty advanced technology and alternative fuel vehicles (AFVs), which has been lacking in the literature. WTW analyses of HDVs becomes increasingly important to understand the fuel consumption and greenhouse gas (GHG) emissions impacts of newly enacted and future HDV regulations from the Environmental Protection Agency and the Department of Transportation’s National Highway Traffic Safety Administration.This paper introduces the new GREET HDV module, which allows for the analysis of fuel consumption, GHG emissions, and air pollutant emissions of 12 conventional (i.e. diesel and/or gasoline) HDV types, including combination long-haul freight trucks, refuse trucks, single-unit delivery trucks, transit buses, and school buses. In addition, the HDV module includes 10 AFVs, including biodiesel, ethanol, natural gas, propane, and hybrid electric, that are currently being either demonstrated or deployed in the United States. Using diesel, gasoline, and natural gas HDVs as examples, we identify the key drivers in HDV WTW analysis including HDV duty-cycle, fuel economy, functional units, and vehicle emission factors.