A detailed reaction mechanism for the combustion of biodiesel fuels has recently been developed by Westbrook and co-workers. This detailed mechanism involves 5037 species and 19990 reactions, which prohibits its direct use in computational fluid dynamic (CFD) applications. In the present work, various mechanism reduction methods included in the Reaction Workbench software were used to derive a semi-detailed biodiesel combustion mechanism, while maintaining the accuracy of the master mechanism for a desired set of engine conditions. The reduced combustion mechanism for a five-component biodiesel fuel was employed in the FORTÉ CFD simulation package to take advantage of advanced chemistry solver methodologies and advanced spray models. Simulations were performed for a Volvo D12C heavy diesel engine fueled by RME fuel using a 72° sector mesh. Predictions were validated against measured in-cylinder parameters and exhaust emission concentrations. The semi-detailed mechanism was shown to be an efficient and accurate representation of actual biodiesel combustion and emissions formation.