Background: US and Brazilian studies indicate that highly active antiretroviral therapy (HAART) has been effective in reducing morbidity and mortality from HIV/AIDS. Differences exist in the adoption and patterns of antiretroviral drug use and in the incidence of AIDS-defining illness (ADI) between the 2 countries, however, and there has not been a direct comparison of clinical response between Brazil and the United States. We sought to determine if there have been differences in the clinical response to HAART from HIV clinical practices in the United States and Brazil. Methods: We compared 2 similarly designed clinical cohorts from Baltimore, Maryland and Rio de Janeiro, Brazil. Patients who started HAART from 1997 to 2004 were compared for HIV-1 RNA suppression and CD4+ T-lymphocyte count change by 1 year of therapy and for development of an ADI up to 6 years of follow-up. A total of 1368 patients from Baltimore and 1045 patients from Rio de Janeiro were studied. Results: There was no difference by location in achieving an HIV-1 RNA level ,400 copies/mL (46.9% in Rio de Janeiro, 50.8% in Baltimore), in the log change in HIV-1 RNA level (21.65 log in Rio de Janeiro, 21.63 log in Baltimore), or in the change in CD4 count (116 cells/mm3 in Rio de Janeiro, 122 cells/mm3 in Baltimore) by 12 months after starting HAART. By Kaplan-Meier analysis and Cox regression adjusted for demographic and clinical prognostic factors, there was no difference by location in development of the first ADI after starting HAART (relative hazard = 1.02; 95% confidence interval: 0.82 to 1.25 for Rio de Janeiro vs. Baltimore). The most commonly occurring ADI in Rio de Janeiro was tuberculosis (27.7% of patients), and the most commonly occurring ADI in Baltimore was esophageal candidiasis (36.8% of patients). Conclusions: There were only minor differences in clinical response to the use of HAART comparing Rio de Janeiro with Baltimore, despite differences in patterns of antiretroviral drug use and ADI incidence. This analysis indicates that HAART can be similarly effective in treating HIV/AIDS in countries with different economies.