The three-dimensional CFD codes KIVA-II and KIVA-3 have been used together to study the effects of intake generated in-cylinder flow structure on fuel-air mixing and combustion in a direct injected (DI) Diesel engine. In order to more accurately account for the effect of intake flow on in-cylinder processes, the KIVA-II code has been modified to allow for the use of data from other CFD codes as initial conditions. Simulation of the intake and compression strokes in a heavy-duty four-stroke DI Diesel engine has been carried out using KIVA-3. Flow quantities and thermodynamic field information were then mapped into a computational grid in KIVA-II for use in the study of mixing and combustion. A laminar and turbulent timescale combustion model, as well as advanced spray models, including wave breakup atomization, dynamic drop drag, and spray-wall interaction has been used in KIVA-II.Simulation of the mixing of the individual fuel jets from the six hole injector shows significant differences in spray penetration and droplet breakup, owing to sizable inhomogeneities in the velocity and turbulence fields present at the time of fuel injection. Comparison of a single fuel jet injected into the realistic in-cylinder flow field with one injected into a uniform flow field which had equivalent average values for all thermodynamic and velocity terms shows marked differences in peak heat release rate, and the timing of the peak itself. Comparison of two fuel jets, injected in to different parts of the same computed flow field having large differences in the local swirl number show that ignition delay is reduced in the case of the higher swirl number. The assertion is made that in the geometry studied, a key role of the large scale flow is the convection and production of turbulence, as seen in differences in predictions of ignition delay and the magnitude and timing of the premixed and diffusion combustion peaks.