Major depressive disorder (MDD) is prevalent after traumatic brain injury (TBI); however, there is a lack of evidence regarding effective treatment approaches. We conducted a choice-stratified randomized controlled trial in 100 adults with MDD within 10 years of complicated mild to severe TBI to test the effectiveness of brief cognitive behavioral therapy administered over the telephone (CBT-T) (n = 40) or in-person (CBT-IP) (n = 18), compared with usual care (UC) (n = 42). Participants were recruited from clinical and community settings throughout the United States. The main outcomes were change in depression severity on the clinician-rated 17 item Hamilton Depression Rating Scale (HAMD-17) and the patientreported Symptom Checklist-20 (SCL-20) over 16 weeks. There was no significant difference between the combined CBT and UC groups over 16 weeks on the HAMD-17 (treatment effect = 1.2, 95% CI: -1.5-4.0; p = 0.37) and a nonsignificant trend favoring CBT on the SCL-20 (treatment effect = 0.28, 95% CI: -0.03-0.59; p = 0.074). In follow-up comparisons, the CBT-T group had significantly more improvement on the SCL-20 than the UC group (treatment effect = 0.36, 95% CI: 0.01-0.70; p = 0.043) and completers of eight or more CBT sessions had significantly improved SCL-20 scores compared with the UC group (treatment effect = 0.43, 95% CI: 0.10-0.76; p = 0.011). CBT participants reported significantly more symptom improvement ( p = 0.010) and greater satisfaction with depression care ( p < 0.001), than did the UC group. In-person and telephone-administered CBT are acceptable and feasible in persons with TBI. Although further research is warranted, telephone CBT holds particular promise for enhancing access and adherence to effective depression treatment.