Twelve-step theory hypothesizes that changes in specific cognitions and behaviors, including adoption of disease model beliefs and involvement in self-help programs, lead to symptom reduction. We examined the role of self-help affiliation in treatment outcome using causal chain analysis. Baseline, end-treatment and follow-up self-help affiliation and substance use were assessed in 252 drug and alcohol abusers attending a community program. Participants were randomly assigned to one of three cognitive-behavioral or 12-Step oriented individual counseling conditions. Participants also were assigned, based on problem severity, to one of three treatment settings (partial hospitalization; intensive outpatient; standard outpatient) that varied according to intensity of additional 12-Step programming. Repeated-measures ANOVA indicated that self-help affiliation increased overall during treatment, particularly in the 12-Step counseling condition (versus cognitive-behavioral), and the partial hospitalization setting (versus standard outpatient). Multiple regression indicated that self-help affiliation was negatively associated with substance use 6 months post-treatment, and that this was not moderated by condition. Self-help affiliation predicted outcome most strongly in the partial hospitalization setting and not at all in outpatient; however, this effect was accounted for by participants' initial problem severity: high-severity patients had poorer outcomes if they failed to increase self-help affiliation, relative to those who increased affiliation and to low-severity patients regardless of affiliation. Results indicate that, in this community-based program, self-help affiliation increased as a function of exposure to 12-Step oriented treatment programming, and significantly predicted better outcome among patients with high levels of problem severity. Implications for future treatment process and dissemination research are discussed.