OBJECTIVES:To investigate the relation of postconcussive complaints, anxiety, and depression with vocational outcome in patients with traumatic brain injury (TBI) of various severities and to assess sex differences. DESIGN:A prospective cross-sectional cohort study. SETTING:Level I trauma center. PARTICIPANTS:Adults (N=242) with TBI of various severity. INTERVENTIONS:Not applicable. MAIN OUTCOME MEASURES:Extended Glasgow Outcome Scale, return to work (RTW), Head Injury Symptom Checklist, and Hospital Anxiety and Depression Scale. RESULTS:In 67% of the patients, complaints were present; 22% were anxious, and 18% were depressed. The frequency of complaints increased significantly with injury severity, in contrast to anxiety and depression. Frequencies of patients with anxiety and depression (9% and 5%) were lower with complete RTW than with incomplete RTW (42% and 37%; P<.001). Patients with minor TBI with complaints were more anxious (50% vs 27%; P<.05) and depressed (46% vs 23%; P<.05) compared with patients with other severity categories and patients with incomplete RTW (67% vs 36% and 60% vs 30%, respectively). A higher percentage of women with minor TBI were depressed (45% vs 13%; P=.01) and had incomplete RTW (50% vs 18%; P<.05) compared with men. Multiple regression analysis showed that injury severity, complaints, anxiety, and depression were all predictive of RTW (explained variance 45%). In all severity categories, anxiety and depression were predictive of RTW, complaints, and sex only for minor TBI. CONCLUSIONS:Anxiety and depression are related to vocational outcome after TBI, with a different profile in the minor TBI category, partly due to sex differences.