Background: In many countries, the opioid agonists, buprenorphine and methadone, are licensed for maintenance treatment of opioid dependence. Many short-term studies have been performed, but little is known about long-term effects. Therefore, this study described over 6 years (1) mortality, retention and abstinence rates and (2) changes in concomitant drug use and somatic and mental health. Methods: A prevalence sample of n = 2,694 maintenance patients, recruited from a nationally representative sample of n = 223 substitution doctors, was evaluated in a 6-year prospective-longitudinal naturalistic study. At 72 months, n = 1,624 patients were assessed for outcome; 1,147 had full outcome data, 346 primary outcome data and 131 had died; 660 individuals were lost to follow-up. Results: The 6-year retention rate was 76.6%; the average mortality rate was 1.1%. During follow-up, 9.4% of patients became "abstinent" and 1.9% were referred for drug-free addiction treatment. Concomitant drug use decreased and somatic health status and social parameters improved. Conclusions: The study provides further evidence for the efficacy and safety of maintenance treatment with opioid agonists. In the long term, the number of opioid-free patients is low and most patients are more or less continuously under opioid maintenance therapy. Further implications are discussed. (C) 2017 S. Karger AG, Basel