Pressure-based and model-based techniques for the control of MFB50 (crank angle at which 50% of fuel mass fraction has burned) have been developed, assessed and tested by means of rapid prototyping (RP) on a 3.0L Euro VI heavy-duty diesel engine. The pressure-based technique requires the utilization of a pressure transducer for each cylinder, which is capable of performing the instantaneous measurement of the in-cylinder pressure, in order to derive its corresponding mass fraction burned and the actual value of MFB50. It essentially consists of a closed-loop approach, which is based on a cycle-by-cycle and cylinder-by-cylinder correction of the start of injection of the main pulse (SOImain), in order to achieve the desired target of MFB50 for each cylinder. The model-based technique, instead, adopts a low-throughput heat release model to predict MFB50; this model is based on an improved version of the accumulated fuel mass approach, which requires the injection rate as input. This control technique is essentially based on the heat release model inversion, in order to identify the optimal value of SOImain that allows the desired target of MFB50 to be achieved cycle-by-cycle. The approach is therefore of the open-loop type. Both control techniques have been developed and assessed by means of Model-in-the-Loop (MiL) and Hardware-in-the-Loop (HiL) techniques, and finally tested on the engine via RP. The experimental tests have been performed at a highly dynamic test bench at Politecnico di Torino. In the MiL phase, the control techniques, which have been developed in Simulink environment, have been assessed and tested on an engine emulator constituted by a GT-power model. In the HiL phase, the control techniques have been integrated on an ETAS ES910 RP device, and tested on a PXI-based real-time engine emulator. Finally, ETAS ES910 RP device has been interfaced with the real engine for the final assessment of the control via rapid prototyping. Both pressure- and model-based control approaches have shown very good performance in terms of MFB50 control, compared to the standard methodology implemented in the ECU, at both steady-state and transient conditions.