Abstract This study aims to advance understanding of in-cylinder combustion processes in medium-speed diesel engines, which are extensively employed in heavy-duty applications where electrification proves inefficient yet remains insufficiently examined in the literature. By modeling a four-stroke engine with dimensions of 210 mm bore and 310 mm stroke, operating at 900 rpm under full load, this research identifies distinct combustion characteristics that differentiate medium-speed engines from their high-speed counterparts. Key findings illustrate that super turbocharging in medium-speed engines enhances the combustion of the fuel–air mixture under elevated temperatures and pressures. Moreover, an increased stroke length promotes gas velocity and turbulence, facilitating fuel atomization and mixing. Notably, rapid fuel ignition occurs near the nozzle due to the high temperature of compressed air, reducing the ignition delay. As a result, the premixed combustion stage nearly disappears, with diffusion combustion dominating, especially pronounced with long-duration injection, a characteristic of medium-speed engines. The study also reveals a more uniform but elevated distribution of nitrogen oxide emissions in medium-speed engines, attributed to prolonged high-temperature conditions that both facilitate their formation. Early stages of diffusion combustion show high concentrations of incomplete combustion products. However, as the combustion process progresses, the conditions favor the complete oxidation of these products at high temperatures, resulting in decreased carbon-based pollutions. In addition, the larger combustion chamber and enhanced turbulence characteristic of medium-speed engines support efficient fuel and air mixing without necessitating the swirl effect required by high-speed engines, diminishing the dependence on wall impingement dynamics for air utilization. Consequently, efficiency optimization strategies for medium-speed engines, emphasizing adjustable injection parameters, encounter fewer constraints than those inherent to the spatial limitations of high-speed engines.