The rate of acute drug-related mortality, or overdose deaths, among prisoners in the immediate post-release period is unacceptably high. Such incidents result from many factors, including decreased tolerance after a period of relative abstinence during imprisonment and the concurrent use of multiple drugs which, with every additional illicit drug consumed in combination with opioids, nearly doubles the risk of death from opioids. Other important factors are the lack of pre-release counselling, post-release follow-up and failure to identify those at risk. Substance dependence is a chronic disorder with high relapse rates and often requires long-term continuous treatment. There is good evidence from trials and cohort studies that opioid substitution treatment reduces the risk of overdose among opioid users. This report identifies the main areas that need to be improved in order to decrease the risk of death. Linking prison health and public health systems closely is essential to mitigating this risk. Recommendations for preventive responses are considered across all levels of the justice system. The report includes a literature review that identifies a substantial body of research from various countries; this research supports the finding that the initial post-release period presents ex-prisoners with a significantly heightened risk of acute drug-related mortality.