Stoichiometric industrial natural gas engines rely on robust design to achieve consumer driven up-time requirements. Key to this design are exhaust components that are able to withstand high combustion temperatures found in this type of natural gas engine. The issue of exhaust component durability can be addressed by making improvements to materials and coatings or decreasing combustion temperatures. Among natural gas engine technologies shown to reduce combustion temperature, dedicated exhaust gas recirculation (EGR) has limited published research. However, due to the high nominal EGR rate it may be a technology useful for decreasing combustion temperature. In previous work by the author, dedicated EGR was implemented on a Caterpillar G3304 stoichiometric natural gas engine. Examination of combustion statistics showed that, in comparison to a conventional stoichiometric natural gas engine, operating with dedicated EGR requires adjustments to the combustion recipe to achieve acceptable engine operation. This work focuses on modifications to the combustion recipe necessary to improve combustion statistics such as coefficient of variance of indicated mean effective pressure (COV of IMEP), cylinder-cylinder indicated mean effective pressure (IMEP), location of 50% mass fraction burned, and 10%–90% mass fraction burn duration. Several engine operating variables were identified to affect these combustion statistics. A response surface method (RSM) optimization was chosen to find engine operating conditions that would result in improved combustion statistics. A third order factorial RSM optimization was sufficient for finding optimized operating conditions at 3.4 bar brake mean effective pressure (BMEP). The results showed that in an engine with a low turbulence combustion chamber, such as a G3304, optimized combustion statistics resulted from a dedicated cylinder lambda of 0.936, spark timing of 45° before top dead center (°bTDC), spark duration of 365 µs, and intake manifold temperature of 62°C. These operating conditions reduced dedicated cylinder COV of IMEP by 10% (absolute) and the difference between average stoichiometric cylinder and dedicated cylinder IMEP to 0.19 bar.