In order to meet IMO Tier III emission regulations, this paper explores the potential of an internal purification method for medium speed marine diesel engines. Based on the test bench experimental data of a high-power medium speed diesel engine, the simulation models of the whole flow and in-cylinder combustion were established using AVL Boost and Fire v2008 software. Various cases of valve timing, Miller cycle, high compression ratio, injection timing, and EGR ratio were designed to investigate their influence on combustion and emissions. The results show that NOx emissions decrease as the inlet valve close timing is advanced, and the premixed combustion peak increases continuously at the same time. This will counteract the function of Miller cycle, which reduces NOx emission; the in-cylinder premixed combustion peak decreases when the geometrical compression ratio is increased, and together with injection timing delay can further reduce NOx emission; by using a moderate Miller cycle combined with moderate EGR technology, NOx emissions can decrease 80%, and soot emissions decrease 20%. This can be a feasible technical combination to meet IMO Tier III regulations about NOx emissions. ©, 2015, Editorial Board of Journal of HEU. All right reserved.