Medium- and Heavy Duty Truck fuel consumption and the resulting greenhouse gas (GHG) emissions are significant contributors to overall U.S. GHG emissions. Forecasts of medium- and heavy-duty vehicle activity and fuel use predict increased use of freight transport will result in greatly increased GHG emissions in the coming decades. As a result, the National Highway Traffic Administration (NHTSA) and the United States Environmental Protection Agency (EPA) finalized a regulation requiring reductions in medium and heavy truck fuel consumption and GHGs beginning in 2014. The agencies are now proposing new regulations that will extend into the next decade, requiring additional fuel consumption and GHG emissions reductions. To support the development of future regulations, a research project was sponsored by NHTSA to look at technologies that could be used for compliance with future regulations.Data presented in this paper detail how engine and vehicle simulation models were developed for current medium and heavy duty vehicles and then validated against available test results. In addition, the paper describes how potential future engine and vehicle technologies were added to the baseline models to simulate future improvements in medium and heavy duty vehicle fuel consumption and GHG emissions. Wherever possible, experimental data was used as inputs to the models or to validate the simulation results. The effect of drive cycle on engine efficiency is also explored.