Large industrial gas turbines for combined heat and power generation normally have axial diffusers leading to the heat recovery steam generator. The diffusers operate with high inlet axial Mach number (0.6) and with a nonuniform inlet total pressure profile from the turbine. Tests have been carried out on a generic highly loaded axial diffuser in a scaled axial diffuser test rig, with different inlet total pressure profiles including those that might be met in practice. The results show that the inlet total pressure profile has a strong effect on the position of flow separation, whereby a hub-strong profile tends to separate at the casing and the tip-strong profile on the hub. Steady computational fluid dynamics (CFD) simulations using the shear stress transport (SST) turbulence model have been carried out based on extensive studies of the best way to model the inlet boundary conditions. These simulations provide good agreement with the prediction of separation in the diffuser but the separated regions often persist too long so that, in this highly loaded case with flow separation, the calculated diffuser pressure recovery can be in error by up to 30%.