It is advantageous to increase the specific power output of diesel engines and to operate them at higher load for a greater portion of a driving cycle to achieve better thermal efficiency and thus reduce vehicle fuel consumption. Such operation is limited by excessive smoke formation at retarded injection timing and high rates of cylinder pressure rise at more advanced timing. Given this window of operation, it is desired to understand the influence of fuel properties such that optimum combustion performance and emissions can be retained over the range of fuels commonly available in the marketplace. Data are examined from a direct-injection single-cylinder research engine for eight common diesel fuels including soy-based biodiesel blends at two high load operating points with no exhaust gas recirculation (EGR) and at a moderate load with four levels of EGR. The high load operating point that incorporates a pilot + main injection strategy shows a reduced sensitivity to fuel ignitibility compared to the high load operating point using only a single injection event. Although ignition delay varies by only 0.5 degCA between the fuels when using the single injection event, the longer ignition delay led to a substantial increase in noise at a constant combustion phasing, and was accompanied by a small increase in smoke and CO emissions. Biodiesel blends increase NOX emissions and decrease CO and smoke emissions at high load, but are otherwise within the range of performance observed for the petroleum-derived fuels. At moderate load, higher CN fuels are more tolerant to EGR due to their better chemical reactivity at retarded injection timing, but all fuels produce comparable thermal efficiency at advanced combustion phasing regardless of EGR. In contrast to the high load conditions, there was no increase in NOX emissions for biodiesel at the moderate load condition. It is concluded that a pilot + main fuel injection strategy at high load is less sensitive to fuel ignitibility differences than a single injection strategy, and that ignitibility differences can result in significant differences in engine noise for the single injection strategy and a the moderate load condition, thus influencing the acceptable injection timing range for each fuel. Apart from CN effects, fuel oxygen content plays an independent role in reducing some emissions. It is therefore recommended that compensation for fuel ignitability and oxygen content be included in combustion control strategies to optimize emissions and performance of future diesel engines.