BACKGROUND: Buprenorphine, a partial mu-agonist and kappa-antagonist, has been proposed as an alternative to methadone for maintenance treatment of opioid dependence, especially for patients with concurrent cocaine dependence or abuse. This study evaluated whether higher maintenance doses of buprenorphine and methadone are superior to lower doses for reducing illicit opioid use and whether buprenorphine is superior to methadone for reducing cocaine use. METHODS: A total of 116 subjects were randomly assigned to 1 of 4 maintenance treatment groups involving higher or lower daily doses of sublingual buprenorphine (12 or 4 mg) or methadone (65 or 20 mg) in a double-blind, 24-week clinical trial. Outcome measures included retention in treatment and illicit opioid and cocaine use as determined by urine toxicology testing and self-report. RESULTS: There were significant effects of maintenance treatment on rates of illicit opioid use, but no significant differences in treatment retention or the rates of cocaine use. The rates of opioid-positive toxicology tests were lowest for treatment with 65 mg of methadone (45%), followed by 12 mg of buprenorphine (58%), 20 mg of methadone (72%), and 4 mg of buprenorphine (77%), with significant contrasts found between 65 mg of methadone and both lower-dose treatments and between 12 mg of buprenorphine and both lower-dose treatments. CONCLUSIONS: The results support the superiority of higher daily buprenorphine and methadone maintenance doses vs lower doses for reducing illicit opioid use, but the results do not support the superiority of buprenorphine compared with methadone for reducing cocaine use.