This research investigates the combustion characteristics and engine performance of a conventional non-ethanol gasoline with a research octane number of 91(RON 91) and a higher reactivity RON80 gasoline under mixing-controlled combustion. The work was conducted in a model year 2013 Cummins ISX15 heavy-duty diesel engine. A split fuel injection strategy was developed to address the long ignition delay and high maximum pressure rise rate for the two gasoline fuels.Using the split fuel injection strategy, steady-state NOx sweeps were conducted at 1375 rpm with a load sweep from 5 to 15 bar BMEP. At 5 and 10 bar BMEP, both gasolines consistently exhibited lower soot levels than ULSD with the reduction more pronounced at 5 bar BMEP. 3-D CFD combustion simulation suggested that the higher volatility and lower viscosity of gasoline fuels can help improve the in-cylinder air utilization and therefore reduce the presence of fuel-rich regions in the combustion chamber. In addition to the NOx sweeps, the 12-mode supplemental emissions test was performed. Results showed that the two gasoline fuels delivered an appreciable soot reduction at low-to-medium load. Hydrocarbon and carbon monoxide emissions were generally higher for the gasoline fuels due to their lower reactivity.Finally, a CFD-guided combustion system design study was conducted for the RON91 gasoline at 1375 rpm and 10 bar BMEP by tailoring its spray and combustion characteristics. Compared to the baseline configuration, simulation suggested that the best configuration led to a 2.3% improvement in fuel consumption.