OBJECTIVES: To perform an economic evaluation of OST in Greece. Individuals wishing to participate in OST are increasing, since only 4,046 opioid-dependent persons were participating in OST programs in 2008, whilst 5,386 who were willing to receive OST were on the waiting list for treatment, with a mean waiting-list time of 6 years. METHODS: Data were gathered from the ΟΚΑΝΑ and EKTEPN, the Greek REITOX (European Information Network on Drugs and Drug Addiction) Focal Point of the European Monitoring Centre for Drugs and Drug Addiction .The total number of  patients included in the analysis was 4046 .  Statistical tests were used to test the homogeneity between treatment programs as well as among geographical areas. Cost-minimization and cost-effectiveness analyses   were conducted to compare methadone and buprenorphine monotherapy with buprenorphine–naloxone. A budget-impact analysis was undertaken in order to estimate the potential costs and savings that could be gained from the expansion of OST programs in Greece. Deterministic and probabilistic sensitivity analyses were performed. To represent the output uncertainty from probabilistic sensitivity analysis scatterplots of 2000 simulated ICERs were produced on the cost-effectiveness plane as well as cost-effectiveness acceptability curves. RESULTS: Cost-minimization analysis predicted that buprenorphine monotherapy is more costly than buprenorphine–naloxone. Cost-effectiveness analyses demonstrated that buprenorphine–naloxone was the dominating therapy in terms of mortality avoidance and completion of treatment. In comparison to methadone, buprenorphine–naloxone reduced the mean cost by 49%; increased by ~1.5-fold the percentage of participants completing their treatment; and reduced by ~2.5-fold the percentage of deaths. Sensitivity analyses did not reverse the findings. CONCLUSIONS: Our findings demonstrated that switching to buprenorphine-naloxone treatment would result in significant savings, reduce waiting lists and increase access to OST.  The introduction of pharmacoeconomic studies in Greece would support rational decision-making in an era of economic recession and uncertainty.