ImportanceThe South Carolina (SC) Healthy Outcomes Plan (HOP) program aimed to expand access to health care to individuals without insurance; it remains unknown whether there is an association between the SC HOP program and emergency department (ED) use among patients with high health care costs and needs.ObjectivesTo determine whether participation in the SC HOP was associated with reduced ED utilization among uninsured participants.Design, Setting, and ParticipantsThis retrospective cohort study included 11 684 HOP participants (ages 18-64 years) with at least 18 months of continuous enrollment. Generalized estimating equations and segmented regression of interrupted time-series analyses of ED visits and charges were conducted from October 1, 2012, to March 31, 2020.ExposuresTime intervals related to the HOP were 1 year before and 3 years after participation.Main Outcomes and MeasuresED visits per 100 participants per month and ED charges per participant per month overall and by subcategory.ResultsThe mean (SD) age of the 11 684 participants in the study was 45.2 (10.9) years; 6293 (54.5%) were women; 5028 (48.4%) were Black participants and 5189 (50.0%) were White participants. Over the study period, the mean (SE) number of ED visits decreased by 44.1%, from 48.1 (5.2) to 26.9 (2.8) per 100 participants per month. The mean (SE) ED charges were reduced to $858 ($46) per participant per month, a decrease from a mean (SE) of $1583 ($88) per participant per month 1 year before HOP implementation. There was an immediate level decrease of 40% (relative risk [RR], 0.61; 99.5% CI, 0.48-0.76; P < .001) from the preenrollment period, with a sustained reduction trend of 8% (RR 0.92; 99.5% CI, 0.89-0.95; P < .001) during the postenrollment period. A level change for ED charges was detected, at a decrease of 40% (RR 0.60; 99.5% CI, 0.47-0.77; P < .001) directly after HOP enrollment with a subsequent downward trend of 10% (RR 0.90; 99.5% CI, 0.86-0.93; P < .001) for the postenrollment period.Conclusions and RelevanceIn this retrospective cohort study, proportions and charges of ED visits by uninsured patients saw immediate and sustained decreases after HOP enrollment. Reducing ED charges may have been driven by decreasing the ED as the primary point of patient care, especially for high-frequency users. These findings have implications for other nonexpansion states seeking to maximize uninsured compensation for low-income populations through improved outcomes.