This article presents the cost-effectiveness results of a randomised controlled trial conducted in two Australian cities. The trial was designed to assess the safety, efficacy and cost-effectiveness of buprenorphine versus methadone in the management of opioid dependence. The trial utilised a flexible dosing regime that was tailored to the clinical need of the patients, with high maximum doses, using the marketed formulation, under double-blind conditions. A total of 405 subjects were randomised to a treatment at one of three specialist outpatient drug treatment centres in Adelaide and Sydney, Australia. The perspective of the cost-effectiveness analysis was that of the service provider and included costs relevant to the provision of treatment. The primary outcome measure used in the economic analysis was change in heroin-free days from baseline to the sixth month of treatment. Treatment with methadone was found to be both less expensive and more effective than treatment with buprenorphine, which suggests methadone dominates buprenorphine. However, statistical testing found that the observed difference between the cost-effectiveness of methadone and buprenorphine treatments was not statistically significant. The results of this study provide useful policy information on the costs and outcomes associated with the use of methadone and buprenorphine and indicate that buprenorphine provides a viable alternative to methadone in the treatment of opioid dependence.