Importance: Opioid-related overdose accounts for almost 80 000 deaths annually across the US. People who use drugs leaving jails are at particularly high risk for opioid-related overdose and may benefit from take-home naloxone (THN) distribution.

Question: What is the population impact of take-home naloxone distribution at jail release to reverse opioid-related overdose among people with opioid use disorders?

Findings: In this decision analytical modeling study, take-home naloxone distribution at jail release was estimated to reduce opioid-related overdose mortality. The presence of willing and capable bystanders at an opioid overdose event was a factor in program effectiveness.

Meaning: Findings of this study suggest that naloxone distribution at jail release is associated with a reduction in opioid-related overdose mortality.