This study experimentally investigates the impact of Miller cycle strategies on the combustion process, emissions, and thermal efficiency in heavy-duty diesel engines. The experiments were conducted at constant engine speed, load, and engine-out NOx (1160 rev/min, 1.76 MPa net IMEP, 4.5 g/kWh) on a single cylinder research engine equipped with a fully-flexible hydraulic valve train system. Early Intake Valve Closing (EIVC) and Late Intake Valve Closing (LIVC) timing strategies were compared to a conventional intake valve profile. While the decrease in effective compression ratio associated with the use of Miller valve profiles was symmetric around bottom dead center, the decrease in volumetric efficiency (VE) was not. EIVC profiles were more effective at reducing VE than LIVC profiles. Despite this difference, EIVC and LIVC profiles with comparable VE decrease resulted in similar changes in combustion and emissions characteristics. Miller cycle operation at constant intake pressure resulted in lower peak cylinder pressures, higher exhaust temperatures and lower EGR requirements compared to the baseline case, albeit with a significant fuel consumption penalty. Increasing intake manifold pressure to match the baseline lambda overcame the fuel consumption penalty, without compromising NOx emissions. As Miller cycle implementation was shown to affect overall turbocharger efficiency (nTC), select EIVC/LIVC profiles were compared to the baseline condition at three different overall turbocharger efficiencies. At the baseline ηTC, Miller cycle profiles reduced peak cylinder pressures and increased exhaust temperatures with minimal BSFC and particulate matter (PM) emission penalties. At high overall turbocharger efficiencies, using Miller cycle offered reduced peak cylinder pressures and elevated exhaust temperatures over conventional intake valve profiles, without compromising BSFC, NOx or PM emissions.