A study of statistical optimization of engine operating parameters was conducted. The objective of the study was to develop a strategy to efficiently optimize operating parameters of diesel engines with multiple injection and EGR capabilities. Previous studies have indicated that multiple injections with EGR can provide substantial simultaneous reductions in emissions of particulate and NOx from heavy-duty diesel engines, but careful optimization of the operating parameters is necessary in order to receive the full benefit of these combustion control techniques. The goal of the present study was to optimize the control parameters to reduce emissions and brake specific fuel consumption. An instrumented single-cylinder heavy-duty diesel engine was used with a prototype mechanically actuated (cam driven) fuel injection system.A mathematical declaration of the optimization goal is stated using an objective function and the optimization process is reduced to a problem of searching for a minimum or maximum on a hypersurface. The variables included in the optimization process included injection pressure, boost pressure, EGR rate, injection timing, and split injection parameters. Using the response surface optimization scheme, the engine could be optimized rapidly, yielding both reductions in emissions consistent with future heavy-duty standards, and also a substantial reduction in fuel consumption compared to the same engine using an electronic unit injector calibrated for 1998 emissions levels.