In a study of 34 human immunodeficiency virus (HIV)-seropositive and 12 HIV-seronegative intravenous drug users with 40 and 14 episodes, respectively, of infective endocarditis (IE), there were no differences between groups in the presentation of IE. Staphylococcus aureus was the infecting microorganism in 75% of the HIV-positive patients and 86% of the HIV-negative patients. Overall survival for the HIV-positive patients was 85% compared with 93% for the HIV-negative patients. Ninety percent of patients with asymptomatic HIV infection survived, whereas 60% of patients in CDC group IV survived (P = .052). In contrast to New Jersey seroprevalence surveys showing HIV antibody in 10%-50% of intravenous drug users, HIV antibody seroprevalence rate in this selected population was 75%. IE in the HIV-seropositive intravenous drug user is essentially the same as in the seronegative user. However, patients with symptomatic HIV infection may be more likely to die from their IE. Intravenous drug users with IE have a greater-than-expected seroprevalence of HIV; the reason remains to be determined.