To our knowledge, the epidemiology of hospital-acquired infections in human immunodeficiency virus (HIV)-infected patients during long-term care has not been reported. For 13 months, we observed HIV-infected patients (50 men and 15 women) in a dedicated 21-bed unit in a long-term-care facility to determine the rate of nosocomial infections. The mean age of the patients was 39 years (range, 22-78 years); 74% of the patients had CD4 cell counts of < 200/mm3. There was a total of 152 infections (24 infections per 1,000 long-term-care days). The factors associated with the occurrence of a nosocomial infection were low CD4 cell counts, poor functional status, and longer duration of stays at the facility. The three most common infections were Clostridium difficile-associated diarrhea, primary bacteremia, and urinary tract infection. Eighteen hospital-manifested opportunistic infections occurred. More than 50% of the cases of bacteremia were due to multidrug-resistant organisms. Nosocomial infections occur commonly in HIV-infected patients in long-term care and thus are important considerations in patient management.