ObjectivesTo determine all-cause and specific-causes mortality, in the years 1999–2008, among opioid-dependent users treated at methadone maintenance treatment (MMT) clinics in Israel and to compare the obtained results with data from relevant studies worldwide. MethodThe records of patients treated at MMT units were linked to the nationwide database of causes of death. Information about the Israeli general population from the Central Bureau of Statistics was used for comparison to match sex and age to the cohort under study. Crude mortality rates (CMRs) per 100 persons per year (PY) and standardized mortality ratios (SMRs) with 95% confidence intervals (CIs) were calculated. ResultsThe overall CMR for MMT users was 1.49/100 PY (CI 1.40–1.59) and was not associated with gender, age at entering MMT, ethnicity, and immigrant status. The leading causes of mortality were sudden/undefined death (0.31/100 PY, CI 0.26–0.35), overdose (0.22/100 PY, CI 0.17–0.27), and cancer (0.15/100 PY, CI 0.12–0.18). The MMT users were 12.2 times more likely to die from all causes than people from the general population. Overall, our estimates were comparable with the figures pooled from relevant studies. ConclusionsThe results suggest that the excess mortality of MMT users is associated with an increased morbidity, which alone or in combination with service-related risks, lead to worse outcomes.