The role of specific psychiatric diagnoses in emergency department use and/or inpatient hospitalizations (acute care) has not been extensively examined among HIV-infected, unstably housed persons. A community-recruited sample of 284 HIV-infected, unstably housed adults completed the Diagnostic Interview Schedule for DSM-IV. One-third of participants screened positive for major depression and stimulant use disorders. Sleeping on the street [adjusted odds ratio (AOR) = 4.21], major depression (AOR = 2.88) and stimulant use disorders (AOR = 4.45) were associated with greater odds of acute care use. Housing and effective treatment of depression and stimulant use disorders may decrease use of acute care services in this population.