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To assess whether the introduction of a prison-based opioid substitution therapy (OST) policy was associated with a reduction in drug-related deaths (DRD) within 14 days after prison release.Linkage of Scotland's prisoner database with death registrations to compare periods before (1996–2002) and after (2003–07) prison-based OST was introduced.All Scottish prisons.People released from prison between 1 January 1996 and 8 October 2007 following an imprisonment of at least 14 days and at least 14 weeks after the preceding qualifying release.Risk of DRD in the 12 weeks following release; percentage of these DRDs which occurred during the first 14 days.Before prison-based OST (1996–2002), 305 DRDs occurred in the 12 weeks after 80 200 qualifying releases, 3.8 per 1000 releases [95% confidence interval (CI) = 3.4–4.2]; of these, 175 (57%) occurred in the first 14 days. After the introduction of prison-based OST (2003–07), 154 DRDs occurred in the 12 weeks after 70 317 qualifying releases, a significantly reduced rate of 2.2 per 1000 releases (95% CI = 1.8–2.5). However, there was no change in the proportion which occurred in the first 14 days, either for all DRDs (87: 56%) or for opioid-related DRDs.Following the introduction of a prison-based opioid substitution therapy (OST) policy in Scotland, the rate of drug-related deaths in the 12 weeks following release fell by two-fifths. However, the proportion of deaths that occurred in the first 14 days did not change appreciably, suggesting that in-prison OST does not reduce early deaths after release.