This work studies the effect and performance of an optimal control strategy on engine fuel efficiency and pollutant emissions. An accurate mean value control-oriented engine model has been developed and experimental validation on a wide range of operating conditions was carried out. A direct optimization method based on Euler’s collocation scheme is used in combination with the above model in order to address the optimal control of the engine. This optimization method provides the optimal trajectories of engine controls (fueling rate, exhaust gas recirculation valve position, variable turbine geometry position and start of injection) to reproduce a predefined route (speed trajectory including variable road grade), minimizing fuel consumption with limited [Formula: see text] emissions and a low soot stamp. This optimization procedure is performed for a set of different [Formula: see text] emission limits in order to analyze the trade-off between optimal fuel consumption and minimum emissions. Optimal control strategies are validated in an engine test bench and compared against engine factory calibration. Experimental results show that significant improvements in both fuel efficiency and emissions reduction can be achieved with optimal control strategy. Fuel savings at about 4% and less than half of the factory [Formula: see text] emissions were measured in the actual engine, while soot generation was still low. Experimental results and optimal control trajectories are thoroughly analyzed, identifying the different strategies that allowed those performance improvements.