AIMS: To quantify the association between opioid agonist treatment (OAT) and overdose death by age group; test the hypothesis that across different age groups, opioid overdose mortality is lowest during OAT with buprenorphine compared with time out of treatment or OAT with methadone; and test associations between OAT and opioid overdose mortality in the presence of chronic circulatory, respiratory, liver, and kidney diseases.

DESIGN: Retrospective observational cohort study using linked administrative data. In New South Wales, Australia, participants were 37,764 people prescribed OAT, 1 August 2002 and 31 December 2017.

MEASUREMENTS: OAT exposure, opioid overdose mortality, and key confounders were measured using linked population datasets on OAT entry and exit, hospitalisation, mental health care, incarceration, and mortality. ICD-10 codes were used to define opioid overdose mortality and chronic disease groups of interest.

FINDINGS: Relative to time out of treatment, time in OAT was associated with lower risk of opioid overdose death across all age groups and chronic diseases. Among people aged 50 years and older, there was weak evidence that buprenorphine may be associated with greater protection against opioid overdose death than methadone. Buprenorphine was associated with greater protection against overdose death than methadone for clients with circulatory diseases, but not liver or kidney diseases.

CONCLUSIONS: Opioid agonist treatment (OAT) appears to reduce mortality risk in people with opioid use disorder who are older or who have physical comorbidities. Opioid overdose mortality during OAT with buprenorphine appears to be lower and reduced in clients with circulatory and respiratory diseases compared with OAT with methadone.