Highly loaded impellers, typically used in turbocharger and gas turbine applications, exhaust an unsteady, transonic flow that is nonuniform across the span and pitch and swirling at angles approaching tangential. With the exception of the flow angle, conflicting data exist regarding whether these attributes have substantial influence on the performance of the downstream diffuser. This paper quantifies the relative importance of the flow angle, Mach number, nonuniformity, and unsteadiness on diffuser performance, through diffuser experiments in a compressor stage and in a rotating swirling flow test rig. This is combined with steady and unsteady Reynolds-averaged Navier–Stokes (RANS) computations. The test article is a pressure ratio 5 turbocharger compressor with an airfoil vaned diffuser. The swirling flow rig is able to generate rotor outflow conditions representative of the compressor except for the periodic pitchwise unsteadiness and fits a 0.86 scale diffuser and volute. In both rigs, the time-mean impeller outflow is mapped across a diffuser pitch using miniaturized traversing probes developed for the purpose. Across approximately two-thirds of the stage operating range, diffuser performance is well correlated to the average impeller outflow angle when the metric used is effectiveness, which describes the pressure recovery obtained relative to the maximum possible given the average inflow angle and Mach number and the vane exit metal angle. Utilizing effectiveness captures density changes through the diffuser at higher Mach numbers; a 10% increase in pressure recovery is observed as the inlet Mach number is increased from 0.5 to 1. Further, effectiveness is shown to be largely independent of the time-averaged spanwise and unsteady pitchwise nonuniformity from the rotor; this independence is reflective of the strong mixing processes that occur in the diffuser inlet region. The observed exception is for operating points with high time-averaged vane incidence. Here, it is hypothesized that temporary excursions into high-loss flow regimes cause a nonlinear increase in loss as large unsteady angle variations pass by from the rotor. Given that straight-channel diffuser design charts typically used in preliminary radial vaned diffuser design capture neither streamtube area changes from impeller exit to the diffuser throat nor vane incidence effects, their utility is limited. An alternative approach, utilizing effectiveness and vane leading edge incidence, is proposed.