This article first explains the conceptual framework and plan of a naturalistic, multisite evaluation of Department of Veterans Affairs (VA) substance abuse treatment programs. It then examines the effectiveness of an index episode of inpatient treatment and the effectiveness of continuing outpatient care and participation in self-help groups. The study was conducted among 3018 patients from 15 VA programs that emphasized 12-Step, cognitive-behavioral (CB), or eclectic treatment. Casemix-adjusted 1-year outcomes showed that patients in 12-Step programs were the most likely to be abstinent, free of substance abuse problems, and employed at the 1-year follow-up. Patients who obtained more regular and more intensive outpatient mental health care, and those who participated more in 12-Step self-help groups, were more likely to be abstinent and free of substance use problems at the 1-year follow-up. These findings support the effectiveness of 12-Step treatment and show that patients with substance use disorders who become more involved in outpatient care and self-help groups tend to experience better short-term substance use outcomes. Subsequent papers in this section focus on the proximal outcomes of treatment, patients with psychiatric as well as substance use disorders, patient-treatment matching effects, and the link between program treatment orientation and patients’ involvement in and the influence of 12-Step self-help groups.