ABSTRACT: Importance:Addressing the social determinants of health has been difficult for health systems to operationalize. Objective:To assess a standardized intervention, Individualized Management for Patient-Centered Targets (IMPaCT), delivered by community health workers (CHWs) across 3 health systems. Design, Setting, and Participants:This 2-armed, single-blind, multicenter randomized clinical trial recruited patients from 3 primary care facilities in Philadelphia, Pennsylvania, between January 28, 2015, and March 28, 2016. Patients who resided in a high-poverty zip code, were uninsured or publicly insured, and who had a diagnosis for 2 or more chronic diseases were recruited, and patients were randomized to either the CHW intervention or the control arm (goal setting only). Follow-up assessments were conducted at 6 and 9 months after enrollment. Data were analyzed using an intention-to-treat approach from June 2017 to March 2018. Intervention:Participants set a chronic disease management goal with their primary care physician; those randomized to the CHW intervention received 6 months of tailored support. Main Outcomes and Measures:The primary outcome was change in self-rated physical health. The secondary outcomes were self-rated mental health, chronic disease control, patient activation, patient-reported quality of primary care, and all-cause hospitalization. Results:Of the 592 participants, 370 (62.5%) were female, with a mean (SD) age of 52.6 (11.1) years. Participants in both arms had similar improvements in self-rated physical health (mean [SD], 1.8 [11.2] vs 1.6 [9.9]; P?=?.89). Patients in the intervention group were more likely to report the highest quality of care (odds ratio [OR], 1.8; 95% CI, 1.4-2.4; risk difference [RD], 0.12; P?