This study compared driving simulation performance after night call and after being off call in 22 medical residents and 1 medical student in a prospective within-subjects counterbalanced design. The results demonstrated an unexpected interaction between call and sex wherein men performed more poorly after night call than women as measured by lane variance and crash frequency. Secondary measures, including caffeine, actigraphy, and subjective total sleep time, did not differ between men and women. Collectively, results of this study and others suggest that medical residents are at risk when driving after a night on call and support the need for resident education to address sleep needs, consequences of sleep disruption, postcall recovery sleep, and countermeasures that may reduce residents' driving risks.