This study examined factors affecting medical service use among HIV-infected persons with a substance abuse disorder. The sample comprised 190 participants enrolled in a randomized trial of a case management intervention. Participants were interviewed about their backgrounds, housing status, income, alcohol and drug use problems, health status and depressive symptoms at study entry. Electronic medical records were used to assess medical service use. Poisson regression models were tested to determine the effects of need, enabling and predisposing factors on the dependent variables of emergency department visits, inpatient admissions and ambulatory care visits. During a two-year period, 71% were treated in the emergency department, 64% had been hospitalized and the sample averaged 12.9 ambulatory care visits. Homelessness was associated with higher utilization of emergency department and inpatient services; drug use severity was associated with higher inpatient and ambulatory care service use; and alcohol use severity was associated with greater use of emergency medical services. Homelessness and substance abuse exacerbate the health care needs of HIV-infected persons and result in increased use of emergency department and inpatient services. Interventions are needed that target HIV-infected persons with substance abuse disorders, particularly those that increase entry and retention in outpatient health care and thus decrease reliance on acute hospital-based services.