Homeless adults use emergency department (ED) services more frequently than other adults, but the relationships between homelessness, health status, outpatient service use, and ED utilization are poorly understood. Data from the Collaborative Initiative to Help End Chronic Homelessness (CICH) were used to compare ED use among chronically homeless adults receiving comprehensive housing, case management, mental health, addiction, and primary care services through CICH at 5 U.S. sites (n = 274) and ED use among comparison group clients receiving generally available community services (n = 116) at the same sites. Multiple imputation was used to account for missing data and differential rates of attrition between the cohorts. Longitudinal models were constructed to compare ED use between the 2 groups during the first year after initiation of CICH services. A mediation analysis was performed to determine the relative contributions of being housed, the receipt of outpatient services, and health status to group differences in ED utilization. Participants receiving CICH services were significantly less likely to report ED use (odds ratio = 0.78, 95% confidence interval [0.65, 0.93]) in the year after program entry. Decreased ED use was primarily mediated by decreased homelessness-not by increased access to other services or health status. This suggests that becoming housed is a key driver of reduced ED utilization and that efforts to provide housing for homeless adults may result in significantly decreased ED use. Further research is needed to determine the long-term effects of housing on health status and to develop services to improve health outcomes.