This report presents CFD simulations of the flow in an S-duct with vortex generators (VGs) added to control the boundary layer separation. The computations are performed with the flow solver EDGE and use is made of two newly implemented boundary conditions and a VG model that makes it possible to investigate several VG configurations without remeshing. The first part of the report deals with the comparison of experimental data and CFD results for the S-duct at several mass flow conditions, with and without VGs. The comparison is essentially made at the Aerodynamic Interface Plane (AIP) where total pressure contours are compared and the distortion indicator DC60 calculated. Overall good agreement is obtained except for the prediction of the DC60. In the second part, an optimization of the VG configuration is performed to improve the quality of the flow at the AIP. The optimization procedure is based on the experimental design process followed by an analysis with the response surface method. An improvement of the DC60 index by 65% is achieved while the total pressure recovery remains constant.