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Linking individuals to community resources in order to help meet health-related social needs, such as food, medications, or transportation, may improve clinical outcomes. However, little is known about the mechanisms whereby such linkage interventions might improve health. The authors conducted a mixed-methods analysis consisting of outcomes from a prospective cohort study of a linkage intervention and a qualitative analysis of case records from participants. The cohort study included intervention participants who first enrolled between December 2014 and March 2015. Participants were excluded if they could not complete the assessment because of illness or language. The authors examined changes in cost-related medication underuse (CRMU), transportation barriers, and food insecurity (FI). For the qualitative analysis, a random sample of 80 participants was selected for electronic health record review – 40 cases who showed clinical improvement (responders) and 40 cases who did not (nonresponders). Themes were extracted by 3 reviewers guided by the immersion/crystallization approach. For the cohort study, 141 individuals were included; 138 (97.9%) completed follow-up. Comparing baseline to follow-up, there were significant reductions in the prevalence of CRMU (from 44.2% to 39.1%, P = .003) and transportation barriers (from 46.3% to 30.2%, P = .001), but not FI (from 40.4% to 38.2%, P = .73). For the qualitative study, emergent themes that helped differentiate responders and nonresponders included acuity of need, resource availability/access, and adequacy of the resource utilized. CRMU and transportation barriers may be important mechanisms by which linkage interventions improve health-related social needs. Patient-centered themes can help guide intervention improvements. [ABSTRACT FROM AUTHOR]