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Purpose: Overdose is a leading cause of death among people who use drugs (PWUDs), but policies to reduce fatal overdose have had mixed results. Summaries of naloxone access and Good Samaritan Laws (GSLs) in prior studies provide limited information about local context. Witnessing overdoses may also be an important consideration in providing services to PWUDs, as it contributes to post traumatic stress disorder (PTSD) symptoms, which complicate substance use disorder treatment., Methods: We aim to estimate the prevalence and correlates of witnessing and responding to an overdose, while exploring overdose context among rural PWUD. The Drug Injection Surveillance and Care Enhancement for Rural Northern New England (DISCERNNE) mixed-methods study characterized substance use and risk behaviors in 11 rural Massachusetts, Vermont, and New Hampshire counties between 2018 and 2019. PWUD completed surveys (n = 589) and in-depth interviews (n = 22)., Findings: Among the survey participants, 84% had ever witnessed an overdose, which was associated with probable PTSD symptoms. Overall, 51% had ever called 911 for an overdose, though some experienced criminal legal system consequences despite GSL. Although naloxone access varied, 43% had ever used naloxone to reverse an overdose., Conclusions: PWUD in Northern New England commonly witnessed an overdose, which they experienced as traumatic. Participants were willing to respond to overdoses, but faced barriers to effective overdose response, including limited naloxone access and criminal legal system consequences. Equipping PWUDs with effective overdose response tools (education and naloxone) and enacting policies that further protect PWUDs from criminal legal system consequences could reduce overdose mortality., (© 2022 National Rural Health Association.)