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Strengths-based strategies to reduce youth violence in low-resource urban communities are urgently needed. Supportive adolescent-adult relationships may confer protection, but studies have been limited by self-reported composite outcomes. We conducted a population-based case-control study among 10- to 24-year-old males in low-resource neighborhoods to examine associations between supportive adult connection and severe assault injury. Cases were victims of gunshot assault injury (n = 143) and non-gun assault injury (n = 206) from two level I trauma centers. Age- and race-matched controls (n = 283) were recruited using random digit dial from the same catchment. Adolescent-adult connections were defined by: (1) brief survey questions and (2) detailed family genograms. Analysis used conditional logistic regression. There were no significant associations between positive adult connection, as defined by brief survey questions, and either gunshot or non-gun assault injury among adolescents with high prior violence involvement (GSW OR = 2.46, 95% CI 0.81-7.49; non-gun OR = 1.59, 95% CI 0.54-4.67) or low prior violence involvement (GSW OR = 0.92, 95% CI 0.34-2.44; non-gun OR = 1.96, 95% CI 0.73-5.28). In contrast, among adolescents with high levels of prior violence involvement, reporting at least one supportive adult family member in the family genogram was associated with higher odds of gunshot assault injury (OR = 4.01, 95% CI 1.36-11.80) and non-gun assault injury (OR = 4.22, 95% CI 1.48-12.04). We were thus unable to demonstrate that positive adult connections protected adolescent males from severe assault injury in this highly under-resourced environment. However, at the time of injury, assault-injured adolescents, particularly those with high prior violence involvement, reported high levels of family support. The post-injury period may provide opportunities to intervene to enhance and leverage family connections to explore how to better safeguard adolescents. [ABSTRACT FROM AUTHOR]