Oxygen availability in brain tissue is closely linked to local hemodynamics and even slight disturbances in the cerebral microcirculation may damage cells due to the brain’s high energy demands. In addition to local cerebral blood flow, knowledge of the oxygen extraction fraction (OEF) is critical when assessing brain tissue oxygenation. A biophysical model that relates the brain’s microvascular hemodynamics to OEF has previously been proposed. Here, we aimed to calibrate and compare this model with OEF measurements determined by [ 15 O]-based positron emission tomography imaging (PET). Local brain hemodynamics were assessed in 68 healthy elderly individuals using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI). Average DSC-MRI-based mean transit time and capillary transit time heterogeneity were compared to PET OEF to calibrate the model parameters. The calibrated biophysical model produced OEF estimates in the range of PET OEF with a moderate correlation (r = 0.31, p = 0.009), albeit with a tendency to overestimate smaller PET OEF values and underestimate larger PET OEF values. We discuss the assumptions made when modeling oxygen transport in measurements of local hemodynamics and in [ 15 O]-based tracer uptake, respectively, and propose that the biophysical model provides a valuable tool to link hemodynamic changes to oxygen uptake in the human brain.