In the present work, different combustion control strategies have been experimentally tested in a heavy-duty 3.0 L Euro VI diesel engine. In particular, closed-loop pressure-based and open-loop model-based techniques, able to perform a real-time control of the center of combustion (MFB50), have been compared with the standard map-based engine calibration in order to highlight their potentialities. In the pressure-based technique, the instantaneous measurement of in-cylinder pressure signal is performed by a pressure transducer, from which the MFB50 can be directly calculated and the start of the injection of the main pulse (SOImain) is set in a closed-loop control to reach the MFB50 target, while the model-based approach exploits a heat release rate predictive model to estimate the MFB50 value and sets the corresponding SOImain in an open-loop control.The experimental campaign involved both steady-state and transient tests. The three control techniques were compared in steady-state tests under various conditions, featuring standard as well as PCCI combustion mode, different kinds of fuels, a disturbance added to the pressure signals from in-cylinder transducers (to simulate the effect of an aged or low-cost pressure transducer) and an injector with a reduced mass flow rate mounted on one cylinder. The behavior of the three controls was tested in transient conditions as well, analyzing in particular fast load and speed ramps.The above mentioned testing conditions were performed to evaluate the robustness of the pressure-based and model-based techniques compared to standard calibration map-based control and their outcomes in terms of engine operation stability.The proposed real-time combustion control techniques provided fuel consumption and emissions in line with the conventional map-based control. In addition, they lead to an improvement in combustion stability, which can be an important issue especially when transient operations are considered or when non-conventional combustion modes, such as PCCI, are implemented.