In this paper, a parametric analysis on the main engine calibration parameters applied on gasoline Partially Premixed Combustion (PPC) is performed. Theoretically, the PPC concept permits to improve both the engine efficiencies and the NOx–soot trade-off simultaneously compared to the conventional diesel combustion. This work is based on the design of experiments (DoE), statistical approach, and investigates on the engine calibration parameters that might affect the efficiencies and the emissions of a gasoline PPC. The full factorial DoE analysis based on three levels and three factors (33 factorial design) is performed at three engine operating conditions of the Worldwide harmonized Light vehicles Test Cycles (WLTC). The pilot quantity (Qpil), the crank angle position when 50% of the total heat is released (CA50), and the exhaust gas recirculation (EGR) factors are considered. The goal is to identify an engine calibration with high efficiency and low emissions. The experiments are conducted on a 2l Volvo Euro 6 diesel engine. The fuels tested are Gasoline RON75 and MK1 diesel. Gasoline RON75 permits operation from low to high engine load conditions. A pilot/main injection strategy is adopted, necessary to control the peak pressure rise rate (PRRmax) to acceptable values and to extend the maximum engine load operating area in PPC. The experimental results show that increasing the EGR rate from 0 to 30%, the net efficiency improves approximately of 1.5% units, due to the shorter combustion duration. For all the conditions examined in PPC, the soot levels are about two times lower than diesel combustion. With a high level of EGR, combined with optimized pilot quantity and combustion phasing, high-efficiency PPC combustion can be achieved without penalties in terms of NOx emissions compared to diesel combustion.