Numerical simulations of in-cylinder soot evolution in the optically accessible heavy-duty diesel engine of Sandia National Laboratories have been performed with the multidimensional conditional moment closure (CMC) model using a reduced n-heptane chemical mechanism coupled with a two-equation soot model. Simulation results are compared to the high-fidelity experimental data by means of pressure traces, apparent heat release rate (AHRR) and time-resolved in-cylinder soot mass derived from optical soot luminosity and multiple wavelength pyrometry in conjunction with high speed soot cloud imaging. In addition, spatial distributions of soot relevant quantities are given for several operating conditions.A broad range of operating conditions has been considered: a sweep in start of injection (SOI) at unchanged top dead center (TDC) ambient conditions and a sweep in TDC temperature at an ambient oxygen volume fraction of 12.7 percent, corresponding to a high level of exhaust gas recirculation (EGR). Ignition delays were captured very well, using unaltered model constants and kinetic parameters. The model was found to reproduce pressure and AHRR traces fairly well, although the premixed portion of combustion was in general slightly underpredicted. Concerning emissions, a quantitative comparison of soot mass evolution is presented. Considering the broad range of conditions the model was capable to reproduce the soot trends well; the predicted peak soot mass agreed within a factor of approximately two for almost all operating conditions considered.Overall, the findings suggest that the presented semi-empirical soot model integrated into the CMC framework is a highly promising approach for the prediction of in-cylinder soot evolution for various diesel engine operating conditions.