Different EGR system layouts (a Long Route, a Short Route, and a combination of the two) were evaluated by means of both numerical simulation and experimental tests. In particular, a one-dimensional fluid-dynamic engine model was built in order to evaluate the potential of a Long Route EGR system as well as the potential of different EGR combinations between Long and Short Route. By means of the one-dimensional model, used as a virtual test bench, the estimations of the NOx emissions, based on the Extended Zeldovich Mechanism (EZM), for the different solutions, were compared and valuable information for the calibration of the coordinated EGR LR, EGR SR and Variable Geometry Turbine (VGT) control systems was obtained. Using the Long Route EGR layout, or a proper combination of LR and SR, substantial reductions of the NOx emissions both under steady state and transient operating conditions were achieved, while the numerical simulation allowed obtaining some fundamental knowledge for controlling the EGR flow rate more accurately.