BACKGROUND Contemporary trends in hospitalization patterns among perinatally HIV-infected (PHIV) patients are unknown. We describe rates and reasons for hospitalizations stratified by age group during 2003-2010 within a large cohort of PHIV patients. METHODS 579 PHIV patients engaged in care at 6 geographically diverse pediatric HIV centers affiliated through the HIV Research Network were included. Modified Clinical Classification Software assigned primary ICD-9 codes into diagnostic categories. Analysis was performed using negative binomial regression with generalized estimating equations. RESULTS There were 699 all-cause hospitalizations. The overall rate for the full cohort was 19.9/100 person-years, and overall rates for 0-4, 5-16 and 17-24 year-olds were 25.1, 14.7 and 34.2/100 person-years, respectively. Declines were seen in unadjusted all-cause rates for the whole group [incidence rate ratio per year, 0.93 (0.87-0.99)] and for 5-16 [0.87 (0.76-0.99)] and 17-24 year-olds [0.87 (0.80-0.95)]. After adjustment for CD4, HIV-1 RNA and demographics, rates were no longer declining. Non-AIDS-defining infections and AIDS-defining illnesses together caused 349 (50%) admissions. Declines in these categories drove the overall declines in unadjusted rates. No increases over time were seen for cardiovascular, renal or any other diagnostic categories. CONCLUSIONS While the declines in hospitalizations are reassuring, continued efforts are needed to address the persistently high infectious and non-infectious morbidity among PHIV patients. Innovative strategies may be most critical for 17-24 year-olds. Lack of increases in cardiovascular and renal admissions provides modest, preliminary reassurance against severe non-infectious complications from longstanding HIV infection and antiretroviral exposure.