Stone J, Degenhardt L, Grebely J, et al. - Many of the harms linked with opioid dependence have been reduced in correlation with opioid agonist treatment (OAT). Utilizing mathematical modelling, researchers here comprehensively examined the overall health advantages of OAT in people who inject drugs in Perry County (KY, US), Kyiv (Ukraine), and Tehran (Iran). A dynamic model of HIV and hepatitis C virus (HCV) transmission, incarceration, and mortality through overdose, injury, suicide, disease-related and other causes was developed and it was calibrated to site-specific data using Bayesian methods. They observed differential contribution of drug-related harms to mortality across settings: overdose contributed 27%–47% (range of median projections) of preventable drug-related deaths over 2020–40, suicide 6–17%, injury 3%–17%, HIV 0%–59%, and HCV 2%–18%. Per findings, drug-related harms can be substantially reduced by OAT, especially where there are HIV epidemics in people who inject drugs. In Tehran, the existing OAT coverage (31%) could have a substantial effect, avoiding 13% of preventable drug-related deaths, but the effect will be minimal (averting < 2% of preventable drug-related deaths) in Kyiv and Perry County because of low OAT coverage (< 4%). Research and investment into achieving higher coverage and provision and longer retention of OAT in prisons and the community are required to maximize the effects.