The authors compared longitudinal treatment outcomes for depressed substance-dependent veterans (N = 206) assigned to integrated cognitive-behavioral therapy plus standard pharmacotherapy (ICBT + P) or 12-step facilitation therapy plus standard pharmacotherapy (TSF + P). Drug and alcohol involvement and depressive symptomology were measured at intake and at 3-month intervals during treatment and up to 1 year posttreatment. Participants in both treatment conditions showed decreased depression and substance use from intake. ICBT + P participants maintained improvements in substance involvement over time, whereas TSF + P participants had more rapid increases in use in the months following treatment. Decreases in depressive symptoms were more pronounced for TSF + P than ICBT + P in the 6 months posttreatment. Within both treatment groups, higher attendance was associated with improved substance use and depression outcomes over time. Initial levels of depressive symptomology had a complex predictive relationship with long-term depression outcomes. Early treatment response predicted long-term substance use outcomes for a portion of the sample. Although both treatments were associated with improvements in substance use and depression, ICBT + P may lead to more stable substance use reductions compared with TSF + P.