We performed an economic evaluation of opioid substitution treatment (OST) in Greece using data from the Greek Organ - ization Against Drugs (OKANA). Cost minimization analysis predicted that buprenorphine monotherapy is more costly than buprenorphine-naloxone therapy. Analyses of cost effectiveness demonstrated that buprenorphine-naloxone was the dominant therapy in terms of mortality avoidance and completion of treatment. Furthermore, compared with methadone, buprenorphine-naloxone reduced the mean cost by 49%; it raised the percentage of participants who completed their treatment ~1.5-fold and reduced the percentage of deaths ~2.5-fold. Budget impact analysis demonstrated that switching to buprenorphine-naloxone treatment would result in significant savings, cut the length of waiting lists, and allow greater access to OST in Greece.