PurposePrior studies evaluated protective factors individually as they relate to fewer drug use risk behaviors and related consequences. This is the first study to examine protective factors as part of a multilevel framework along a risk continuum among women involved in the criminal legal system who use drugs. This study describes factors within the socio-ecological framework that are protective against engaging in injection drug use and experiencing nonfatal overdose. MethodData were collected from 900 women with a history of opioid use disorder who were incarcerated and enrolled in the National Institutes of Health/National Institute on Drug Abuse–funded Justice Community Opioid Innovation Network cooperative. Analysis focused on the relationship among individual, interpersonal, and community- or institutional-level protective factors associated with not injecting drugs and not experiencing an overdose in the 90 days before incarceration using multinomial logistic regression. FindingsFindings from this study suggest that, even among a sample of women who use drugs, there are a number of factors associated with being less likely to report higher-risk injection behavior and/or overdose experiences at the individual level (age, religiosity, and less polysubstance use), interpersonal level (not having a partner who injects drugs), and community or institutional level (fewer months incarcerated, less treatment utilization, and less enacted stigma by health care workers). ConclusionsFindings from this study underscore the importance of being able to target prevention interventions to women at different stages of substance use severity and to capitalize on protective factors for those at lower-risk levels to reduce the trajectory of risk to injection practices and overdose experiences.