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Cryptococcus neoformans is a common opportunistic infection in adults with acquired immunodeficiency syndrome (AIDS), but cryptococcal infection (CI) has also been recognized in HIV-negative patients. Despite the fact that many studies were conducted in adults, limited data exist for pediatric patients.The Pediatric Health Information System, a database containing administrative information from 42 United States children's hospitals, was used to identify children admitted for the treatment of CI between 2003 and 2008. All pediatric inpatients less than 19 years of age who received an ICD-9 code for cryptococcosis or cryptococcal meningitis (CM) were included. Data regarding presence of underlying medical conditions, antifungal therapies administered, and hospital discharge disposition were evaluated.A total of 63 cases of CI were identified, for a CI admission frequency of 6.2 cases per million hospitalizations. Most patients (63.5%) had an underlying immunocompromising medical condition, whereas 21% were immunocompetent and 16% were infected with HIV. Cryptococcosis not involving the central nervous system was more common than CM (62% vs. 38%). Most patients received a combination of fluconazole, amphotericin, and flucytosine in their treatment regimen; however, 9 patients received no antifungal medications. The overall in-hospital case fatality rate was 9.5%.The majority of pediatric cryptococcosis occurred in non–HIV-infected patients. However, most patients had other immunocompromising medical conditions. Patients with CM usually received therapy in accordance with the Infectious Disease Society of America guidelines for adults, but patients with non-CM were more likely to receive therapies not supported by these guidelines.