Key PointsQuestionWas South Carolina’s Healthy Outcomes Plan (HOP) associated with a change in emergency department (ED) visits for uninsured patients with high health care costs and needs?FindingsIn this cohort study that included 11 684 HOP participants, a statistically significant 3-year 44.1% reduction in ED service use, with an estimated net reduction in ED charges of $725 per participant, was observed.MeaningThese findings suggest that state-funded hospital-community partnerships that address access to behavioral health care and the safety net, patient activation, and the social determinants of health would benefit other states.