OBJECTIVES: To compare the occurrence of AIDS as well as the sociodemographic and clinical profiles of AIDS patients in Puerto Rico before and after the introduction of highly active antiretroviral therapy (HAART) and the privatization of the island’s public health care system. METHODS: We compared the incident AIDS cases for two three-year periods, 1992-1994 and 1998-2000, in four populations: (1) entire United States, (2) Puerto Rico, (3) Bayamón Health Region (located in north-central Puerto Rico, it includes 11 of the island’s 78 municipalities), and (4) an HIV cohort enrolled at the Universidad Central del Caribe (UCC) School of Medicine. The UCC is located in Bayamón, Puerto Rico, within an academic medical complex that houses the teaching hospital (Ramón Ruíz Arnaú University Hospital), the ambulatory health care facilities (Immunology Clinics) for patients with HIV, and administrative buildings. This represents the major government-sponsored health care infrastructure within the Bayamón Health Region. RESULTS: Incident AIDS declined substantially between the two periods in each of the four populations studied. The 48.1% decline in Puerto Rico exceeded the 40.9% decline in the United States. The decline in Puerto Rico likely resulted from increased availability and implementation of HAART and the delivery of health care to HIV/AIDS patients in an integrated fashion within each regional ambulatory clinic. In spite of this improvement, the absolute number of patients with AIDS on the island remains high. Substantial resources for treatment and prevention are required. The proportion of new AIDS cases was lower among women, persons 40 years of age or older, the less educated, and those living alone. Injection drug use remains the predominant mode of transmission in Puerto Rico. CONCLUSIONS: Further gains in Puerto Rico’s fight against AIDS will depend on the island’s ability to reduce the transmission that occurs through injection drug use; the use of HAART on a larger number of vulnerable patients, particularly intravenous drug users; educational interventions to improve medication compliance in certain risk groups; and specific measures aimed at decreasing the rate of injection drug use.