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The aim of this retrospective study is to use existing epidemiological data on patients in methadone maintenance treatment in Split-Dalmatia County from 2001 to 2015 to evaluate the substitution treatment system and policy of opiate addicts treatment, the epidemiological trend, and risk of overdose mortality. In addition, we would like to highlight the problem of poor control of methadone therapy and thus the possibility of selling methadone. The result is a greater number of deaths caused by methadone in people who were not in methadone therapy.The research included data collected from 3189 patients who had been in the drug abuse treatment program in Split-Dalmatia County during 2001–2015 and data gathered from autopsy examinations of patients in Split-Dalmatia County with emphasis on data for 186 overdosed patients during research period.The total number of patients in the methadone treatment program in Split-Dalmatia County during the research period, except in 2005 and 2006, has been stable, while the number of new opiate patients, being in first-time treatment, decreased by 62.5%. The number of addicts who were in a long-term maintenance program has increased by 198%, whereas the number of addicts who were in a short-term detoxification treatment has decreased by 96.4%. According to results obtained from performed autopsies, 186 death cases were determined as overdoses. Methadone was found in 56 of those cases and was declared as the cause of death in 39 cases (70%). Of the total number of autopsied patients with diagnosed methadone overdose, only 23 (59%) had been recorded to receive methadone therapy in Public Health Institute of Split-Dalmatia County database.The results of this study show the favorable epidemiological trend because of the decreasing number of new opiate patients in treatment. The retention of opiate patients in substitution therapy indicates the effectiveness of methadone maintenance programs. Our research did not determine any influence of methadone substitution therapy on an increasing risk of specific (overdose) mortality.