The association of depression and successful smoking cessation efforts is inconsistent. We test the hypothesis that higher levels of depression complicate efforts to quit smoking in a methadone-maintained (MM) population offered nicotine replacement and a brief behavioral intervention. We recruited 383 participants from 2/02 to 5/04; 340 (88.8%) were assessed at follow- up. Current depressive symptoms were measured using the Psychiatric Diagnostic Screening Questionnaire (PDSQ). Participants were 53% male, 78% Caucasian, with a mean MM duration of 153 weeks. Twenty-seven percent met PDSQ screening criteria for Major Depressive Disorder (MDD). Participants with higher levels of depressive symptoms were significantly less likely to set a quit date (p = .02) but depression was not associated significantly with motivation to quit smoking at baseline, time to first cigarette, or any behavioral indicator of smoking during the follow-up period. Depressive symptoms have little influence on smoking cessation outcomes in this population.