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Major improvements in disease progression among HIV-infected children have followed the adoption of combination antiretroviral therapy.We examined trends in hospitalization rates between 1990–2002 among 3927 children/youths with perinatal HIV infection, ranging in age from newborn to 21 years. We used Poisson regression to test for trends in hospitalization rates by age and year; binomial regression to test for trends in intensive care unit (ICU) admissions and hospitalization at least once and more than once, by age and year; and multivariate logistic regression to examine factors associated with hospitalization, ICU admission, and hospitalization longer than 10 days.Statistically significant downward trends in hospitalization rates and multiple hospitalizations were observed in all age groups from 1990–2002. The proportion of HIV-infected children/youths who were hospitalized at least once declined from 30.4% in 1990 to 12.9% in 2002, with a steady decline occurring after 1996, when the U.S. Public Health Service issued guidelines recommending triple-drug antiretroviral therapy (triple therapy) for HIV-infected children. ICU admissions declined significantly in all age groups except among children younger than 2 years. Logistic regression results indicated that black and Hispanic children/youths were significantly more likely to be hospitalized than white children/youths and that children/youths receiving triple therapy were significantly more likely to be hospitalized than therapy-naive children; the latter association was not observed among children monitored from 1997–2002.Substantial reductions in rates of hospitalization, multiple hospitalizations, and ICU admission have occurred among HIV-infected children/youths from 1990–2002, particularly after 1996, with increased use of triple therapy.