To investigate the frequency and risk factors of major depressive disorder (MDD) after mild to moderate traumatic brain injury (TBI), 69 TBI and 52 general trauma (GT) patients were prospectively recruited and studied at 3-months postinjury. There was a nonsignificant difference in the proportion of MDD patients in the TBI and GT groups. Therefore, a composite MDD group (TBI and GT patients) was compared to patients who were nondepressed. Female gender was related to MDD, but no other risk factors were identified. MDD was associated with disability (Glasgow Outcome Scale, Community Integration Questionnaire) and cognitive impairment. MDD was comorbid with posttraumatic stress disorder. Implications for postacute management of mild to moderate TBI are discussed.