Charge boosting strategy plays an essential role in improving the power density of diesel engines while meeting stringent emissions regulations. In downsized two-stage turbocharged engines, turbocharger matching is critical to achieve desired boost pressure while maintaining sufficiently fast transient response. A numerical simulation model is developed to evaluate the effect of two-stage turbocharger configurations on the perceived vehicle acceleration. The simulation model developed in GT-SUITE consists of engine, drivetrain, and vehicle dynamics sub-models. A model-based turbocharger control logic is developed in MATLAB using an analytical compressor model and a mean-value engine model.The components of the two-stage turbocharging system evaluated in this study include a variable geometry turbine in the high-pressure stage, a compressor bypass valve in the low-pressure stage and an electrically assisted turbocharger in the low-pressure stage. Simulation results show excellent agreements with the test data. The results also indicate that the maximum acceleration and the time needed to reach the maximum can be improved by more than 25%, and more desirable linear acceleration profile can be achieved if a variable geometry turbine and a larger compressor are used in the high-pressure stage and a compressor bypass valve in the low-pressure stage. It is also found that the perceived vehicle acceleration has a strong correlation with the rate of turbocharger speed increase in the low-pressure stage. The observers predict the turbocharger speed and the exhaust gas temperature within 5% errors. The GTSUITE simulation model is also used for observer evaluation and control strategy development.