Objective: To evaluate predictors of non-return to work (nRTW) among social, demographic, clinical, and psychiatric variables after severe traumatic brain injury (TBI) in a cohort of Brazilian patients. Methods: Prospective study. Forty-three community-dwelling individuals treated at a Level I trauma center at the time of TBI were evaluated 18 months after trauma. Measures included DSM-IV-TR criteria for personality changes after TBI and Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) to assess psychiatric diagnosis. Hospitalization variables included Glasgow Coma Scale scores, pupil examination findings, associated limb trauma, Marshall computed tomography classification, and blood glucose levels. Results: After multiple logistic regression analysis, only the diagnosis of personality changes was found to be independently associated with nRTW, with an adjusted odds ratio of 10.92 (p = 0.02, 95% confidence interval 1.41-84.28). Conclusions: In this study, personality changes were an independent predictor of nRTW after severe TBI. Ways to predict risk factors associated with personality changes after severe brain injury could aid in identification of early and effective interventions that might ease the burden associated with this condition.