In support of the Daimler SuperTruck I team’s 55% brake thermal efficiency (BTE) pathway goal, researchers at Oak Ridge National Laboratory performed an experimental investigation of the potential efficiency and emissions benefits of dual-fuel advanced combustion approaches on a modified heavy-duty 15-L Detroit™ DD15 engine. For this work, a natural gas port fuel injection system with an independent injection control for each cylinder was added to the DD15 engine. For the dual-fuel strategies investigated, 65%–90% of the total fuel energy was supplied through the added port fuel injection natural gas (NG) fueling system. The remaining fuel energy was supplied by one or more direct injections of diesel fuel using the production high pressure diesel fueling system. The production DD15 air handling system and combustion geometry were unmodified for this study. Efficiency and emissions with dual-fuel strategies including both low temperature combustion (LTC) and non-LTC approaches such as dual fuel direct-injection were investigated along with control authority over combustion phasing. Parametric studies of dual-fuel NG/diesel advanced combustion were conducted in order to experimentally investigate the potential of high-efficiency, dual-fuel combustion strategies to improve BTE in a multi-cylinder engine, understand the potential reductions in engine-out emissions, and characterize the range of combustion phasing controllability. Characterization of mode transitions from mixing-controlled diesel pilot ignition to kinetically controlled ignition is presented. Key findings from this study included a reproducible demonstration of BTE approaching 48% at up to a 13-bar brake mean effective pressure with significant reductions in engine-out NOx and soot emissions. Additional results from investigating load transients in dual-fuel mode and initial characterization of particle size distribution during dual-fuel operation are presented.