Objective: To examine the utility of the Neurobehavioral Functioning Inventory (NFI) for diagnosing depression in a rehabilitation setting. Design: In a prospective study, a structured clinical interview (Structured Clinical Interview for DSM-IV-TR) was used to identify DSM-IV-defined major depressive disorder (MDD) symptoms among patients with traumatic brain injury (TBI). NFI Depression scale items were compared with DSM-IV diagnosis obtained by the Structured Clinical Interview for DSM-IV Axis I Disorders. Setting: Outpatient neuropsychology clinic at a university hospital, private outpatient physical medicine and rehabilitation clinic, and a long-term specialized living assistance program. Participants: Participants consisted of 78 patients with TBI who were at least 3 months postinjury and 18 years of age or older. Main Outcome Measures: Structured Clinical Interview for DSM-IV Axis I Disorders and the NFI. Results: Psychiatric diagnostic interview with the Structured Clinical Interview for DSM-IV Axis I Disorders indicated that 50% of patients with TBI in our sample had at least one of the following in their lifetime: MDD, MDD due to general medical condition, dysthymia, or adjustment disorder with depressed mood. Thirty percent met diagnostic criteria for current MDD with or without general medical condition. Analyses of the NFI items revealed that individuals with depression endorsed greater levels of problems than did those without depression on 14 of the 32 items related to the DSM-IV symptom domains for depression (P < .00156 with Bonferroni correction). In predicting the diagnosis of depression using individual NFI items, the classification rate based on the Random Forests estimate was 83%. Conclusion: Findings indicate that the NFI items differentiated between depressed and non-depressed patients with TBI. Imposing minimal burden on patients and staff, the NFI appears to have good predictive value in diagnosing major depression. In clinical practice and research, the NFI is a potentially valuable screening tool for identifying major depression in persons with TBI. © 2005 Lippincott Williams & Wilkins, Inc.