Engine experiments were performed on a single-cylinder heavy-duty engine at relatively high loads to investigate the regions where the combustion characteristics are unchanged regardless of the fuel octane number. Primary Reference Fuels (PRFs) and three different commercial fuels with RON values ranging from 0 to 100 were tested in this study. A sweep of net indicated mean effective pressure (IMEPNet) of 5 to 20 bar, absolute intake pressure of 1.5 to 2.8 bar, exhaust gas recirculation (EGR) of 0 to 40%, and fuel injection pressure of 700 to 1400 bar were performed to investigate the combustion characteristics, ignition delay time, combustion duration, efficiency, and emissions. At the highest load point (IMEPNet = 20 bar), all the fuels burn as in conventional diesel combustion. Despite the wide range of octane numbers, all fuels had similar ignition delay time, combustion duration, indicated efficiency, and emissions at 10 to 20 bar IMEPNet. It follows that CI mode is the only realistic option at high load and pressure points. All fuels showed similar combustion duration and emission levels behavior as a function of EGR. The present study shed light on the load threshold above which the combustion characteristics of fuels are close enough to consider the engine as ‘fuel flexible’.