Many recent studies have shown that the Reactivity Controlled Compression Ignition (RCCI) combustion strategy can achieve high efficiency with low emissions. However, it has also been revealed that RCCI combustion is difficult at high loads due to its premixed nature. To operate at moderate to high loads with gasoline/diesel dual fuel, high amounts of EGR or an ultra low compression ratio have shown to be required. Considering that both of these approaches inherently lower thermodynamic efficiency, in this study natural gas was utilized as a replacement for gasoline as the low-reactivity fuel. Due to the lower reactivity (i.e., higher octane number) of natural gas compared to gasoline, it was hypothesized to be a better fuel for RCCI combustion, in which a large reactivity gradient between the two fuels is beneficial in controlling the maximum pressure rise rate.The multi-dimensional CFD code, KIVA3V, was used in conjunction with the CHEMKIN chemistry tool and a Nondominated Sorting Genetic Algorithm (NSGA-II) to perform optimization for a wide range of engine operating conditions. Engine design parameters that were controlled by the genetic algorithm include the fraction of total fuel that is premixed (methane), the timing of the two diesel injections, the amount of diesel in each injection, the diesel fuel injection pressure, and the EGR percentage. The objective of the optimization was to simultaneously minimize soot, NOx, CO, and UHC emissions, as well as ISFC and ringing intensity. A broad load/speed range was investigated; six operating points from 4 to 23 bar IMEP and 800 to 1800 rev/min were optimized. These load/speed combinations represent typical heavy-duty engine conditions. Using the stock compression ratio of 16.1, it was determined that operation up to 13.5 bar IMEP could be achieved with no EGR, while still maintaining high efficiency and low emissions. The study also examined the sensitivity of RCCI combustion at high load to injection system parameters. The results emphasize that precise injection control is needed for combustion control.