Case management (CM) coordinates care for persons with complex health care needs. It is not known whether CM is effective at improving biological outcomes among homeless and marginally housed persons with human immunodeficiency virus (HIV) infection. Our goal was to determine whether CM is associated with reduced acute medical care use and improved biological outcomes in homeless and marginally housed persons with HIV. We conducted a prospective observational cohort study in a probability-based community sample of HIV-infected homeless and marginally housed adults in San Francisco, California. The primary independent variable was CM, defined as none or rare (any CM in ⩽25% of quarters in the study), moderate (>25% but ⩽75%), or consistent (>75%). The dependent variables were 3 self-reported health service use measures (receipt of primary care, emergency department visits and hospitalizations, and antiretroviral therapy adherence) and 2 biological measures. In multivariate models, CM was not associated with increased primary care, emergency department use, or hospitalization. Moderate CM, compared with no or rare CM and was not associated with geometric HIV load. The authors conclude that CM may be a successful method to improve adherence to antiretroviral therapy and biological outcomes among HIV-infected homeless and marginally housed adults. (Authors)