An engine-aftertreatment computational model was developed to support in-loop performance simulations of tailpipe emissions and fuel consumption associated with a range of heavy-duty (HD) truck drive cycles. For purposes of this study, the engine-out exhaust dynamics were simulated with a combination of steady-state engine maps and dynamic correction factors that accounted for recent engine operating history. The engine correction factors were approximated as dynamic first-order lags associated with the thermal inertia of the major engine components and the rate at which engine-out exhaust temperature and composition vary as combustion heat is absorbed or lost to the surroundings. The aftertreatment model included catalytic monolith components for diesel exhaust oxidation, particulate filtration, and selective catalytic reduction of nitrogen oxides (NOx) with urea. Both the engine and aftertreatment models have been calibrated with dynamometer measurements from a commercial 2010-certificated 15-L Cummins diesel engine. Simulations with the combined engine and aftertreatment models above appear to reveal important trends among the fuel efficiency, emissions control, power demand for HD trucks under realistic drive cycle conditions. Thus, this type of computational simulation appears to have significant value in choosing among options for HD vehicle design and operation.