Large-eddy simulations (LES) of turbulent spray combustion in internal combustion engines are conducted with a new hybrid Eulerian-Lagrangian methodology. In this methodology, the Eulerian filtered compressible gas equations are solved in a generalized curvilinear coordinate system with high-order finite difference schemes for the turbulent velocity and pressure. However, turbulent mixing and combustion are simulated with the two-phase compressible scalar filtered mass density function (FMDF) and Lagrangian spray models. The LES/FMDF model is used for simulation of in-cylinder turbulent flow and spray mixing and combustion in three flow configurations: (1) a poppet valve in a sudden expansion, (2) a simple piston-cylinder assembly with a stationary valve, and (3) a realistic single-cylinder, direct-injection spark-ignition (DISI) engine. The flow statistics predicted by the LES model are shown to compare well with the available experimental data for (1) and (2). The computed in-cylinder flow for the third configuration shows significant cycle-to-cycle variations. The flow in the DISI engine is also highly inhomogeneous and turbulent during the intake stroke, but becomes much more homogeneous and less turbulent in the compression stroke. Simulations of spray, mixing and combustion in the DISI engine indicate the applicability of the LES/FMDF model to internal combustion engines and other complex combustion systems. (C) 2013 Elsevier Ltd. All rights reserved.