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Background and Objectives: The present study evaluated the effectiveness of a single clinician delivered brief intervention (BI) to reduce problem alcohol use and illicit substance use in an opiate-dependent methadone maintained cohort of patients attending for treatment. Methods: Four addiction treatment centers were randomly assigned to either treatment as usual (TAU; control group) or BI (intervention group). Clinicians screened patients using the alcohol, smoking, and substance involvement screening test (ASSIST) screening tool at baseline and again at three-month follow up. Fidelity checks were performed to ensure that training was delivered effectively and uniformly across all study sites. Feasibility of administering a BI within daily practice was assessed through intervention fidelity checks, patient satisfaction questionnaires and process evaluation. Results: A total of 465 patients were screened (66% of the overall eligible population) with a total of 433 (93%) ASSIST positive cases. Randomization was effective, with no differences in the control versus the intervention arms at baseline for key demographic or clinical indicators including substance us. There was a statistically significant difference between global risk score for the intervention (x = 39.36, sd = 25.91) group and the control group (x = 45.27, SD = 27.52) at 3-month follow-up (t(341) = −2.07, p <.05). Conclusions: This trial provides the first evidence that a single clinician delivered BI can result in a reduction in substance use within a methadone maintained opiate-dependent cohort, and this effect is sustained at three month follow up. [ABSTRACT FROM AUTHOR]