Aims: To describe deaths in prison in a cohort of opioiddependent people, and examine associations between receipt of opioid substitution therapy (OST) and risk of death while in prison. Methods: We linked state-wide OST data to incarceration and mortality data. We calculated crude mortality rates (CMR) for allcause and unnatural (suicide, drug-induced, violent and injury) deaths in prison, and used Cox regression to assess adjusted associations between death and receipt of OST. Rates and hazard ratios were calculated for the entirety of time in prison, and for the first four weeks in prison. Results: The cohort comprised 16,715 opioid-dependent people who had been incarcerated. Fifty-one people died in prison. Compared to periods of time in OST, all-cause and unnatural mortality rateswere significantly higherwhile not in OST (all-cause rate ratio (RR): 4.1; 95% confidence interval (CI): 2.1, 8.0; unnatural death RR: 6.7; 95% CI: 2.6, 17.3). Compared to time out of OST, the hazard of all-cause deathwas 74% lowerwhile in OST (adjusted hazard ratio (AHR): 0.26; 95% CI: 0.13, 0.50), and the hazard of unnatural death was 87% lower while in OST (AHR: 0.13; 95% CI: 0.05, 0.35). In the first fourweeks of incarceration, compared to periods in OST, all-cause mortality was 16.6 (95% CI: 2.2, 124.9) times higher, and unnaturalmortalitywas14.0 (95%CI: 1.8, 107.9) timeshigherwhen not in OST. Compared to periods not in OST, the hazard of all-cause death during the first 4weeks of incarcerationwas 94% lowerwhile in OST (AHR: 0.06; 95% CI: 0.01, 0.48), and the hazard of unnatural death was 93% lower while in OST (AHR: 0.07; 95% CI: 0.01, 0.53). Conclusions: Ensuring a high coverage of OST in correctional facilities will help to minimize deaths, particularly unnatural deaths, among opioid-dependent prisoners. Timely access to OST while incarcerated is critical to realizing this benefit. Financial Support:NationalHealthandMedicalResearchCouncil.