SummaryDuring a 7-year period, 32 patients withPseudomonas aeruginosainfection were identified on an HIV treatment service at a university-affiliated teaching hospital. The number of cases increased from 2 in 1986 to 13 in 1992. Affected patients had evidence of advanced HIV infection. In those treated with antiretroviral therapy, 96% of infections occurred > 1 year after initial presentation with HIV disease. Eighteen cases of pneumonia and 14 nonpulmonary (central venous access device, soft tissue, middle ear-mastoid, corneal, and peritoneal) infections were seen. Comparison with matched controls identified use of a central venous access device and administration of aerosolized pentamidine, corticosteroids, or ganciclovir as risk factors for infection (odds ratios, 5.3, 6.5, 15.0, and 9.0, respectively;p= 0.004, 0.007, 0.02, and 0.02, respectively). Seventy-five percent of cases had community onset, but time since last hospital discharge was significantly shorter in study patients than in controls (mean difference, −85 days; 95% confidence interval, −24 to - 146;p= 0.01). Among evaluable cases, outcome was fatal (survival ≈30 days) in 2 of 16 (13%) patients in whom initial antibiotic therapy was appropriate and 8 of 14 (57%) patients in whom initial therapy was not appropriate (p= 0.016). Ten recurrent infections were seen in 8 of 21 patients who survived the initial infection. Median survival after onset of infection was only 80 days.Pseudomonas aeruginosainfection is an increasingly frequent, severe complication of advanced HIV disease. Several treatment and prevention strategies used in the management of advanced HIV disease are associated with an increased risk of infection.