This study examined the effect of syringe exchange program setting on the injection practices, health status, and health service utilization patterns of injection drug users (IDUs) recruited from a public urban hospital. One hundred sixty-six participants were randomized to either community- or hospital-based syringe exchange services. Poisson regression models were used to compare service utilization between groups. In both conditions, risky drug use practices decreased, and physical health functioning improved over time. Hospital-based syringe exchange program (SEP) attendees had 83% more inpatient admissions (p < .0001) and 22% more ambulatory care visits (p < .0001) than those assigned to the community-based SEP condition. Syringe exchange services that are integrated into public hospital settings may serve as a valuable strategy to engage hard to reach IDU populations in behavioral interventions designed to reduce HIV risk transmission behaviors and increase access to, or engagement in, the use of secondary and tertiary preventive medical care.