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Illicit opioid use and opioid-involved overdose mortality are spatially concentrated. Previous research has examined how the geographic patterning of overdose mortality reflects variation in risk factors for overdose (e.g. illicit substance use and poverty) and the local availability of formal harm reduction resources (e.g. naloxone distribution sites). However, the spatial concentration of illicit opioid use may also protect against opioid-related mortality by fostering informal harm reduction collective efficacy (IHRCE)—a sense of community among illicit opioid users that (1) promotes awareness of safer opioid use techniques, (2) shelters users against feelings of isolation and worthlessness, and (3) encourages more effective responses to opioid overdose events. While concentrated disadvantage may lead to increased illicit substance use and riskier use behavior—and thus higher overall rates of overdose mortality—it may also selectively protect against opioid use-related fatality by fostering IHRCE. This paper proposes a study using data from the U.S. Census, the National Survey on Drug Use and Health, the Project on Human Development in Chicago Neighborhoods, Chicago police records, and the Cook County Medical Examiner’s office to examine whether, net of other predictors, illicit opioid use leads to fewer opioid-related fatal overdoses in neighborhoods with denser populations of illicit opioid users.