Among military personnel, posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and a history of traumatic brain injury (TBI) are frequently reported, highlighting the need for treatment outcome research with this population. This study examined the influence of the presence or absence of comorbid MDD on the outcome of a residential treatment program at the midpoint and end of the program for 47 male veterans with PTSD and a history of TBI. Results demonstrated significant decreases of self-reported symptoms on the PTSD Checklist-Stressor Specific Version (PCL-S; MDD, d = 1.19; No MDD, d = 1.17) and the Beck Depression Inventory–II (BDI-II; MDD, d = 0.98; No MDD, d = 1.09) following treatment for both groups. There were no differences in the rate of symptom reduction between groups. Individuals who also met criteria for MDD at pretreatment, however, evidenced higher scores on symptom measures at all assessment time points (ds = 0.60–1.25).