BACKGROUND: Infective endocarditis in children is rare, and most reports describe the experience in referral centers. The purpose of our study was to assess the characteristics of children with infective endocarditis in a large national sample. METHODS AND RESULTS: We analyzed hospital discharge records with International Classification of Diseases, ninth revision, codes indicating infective endocarditis among admissions of patients <21 years of age in the Kids' Inpatient Databases 2000 and 2003; analyses for the 2 years were combined. In 1588 hospitalizations, the age distribution was bimodal, with peaks in infancy and late adolescence. The organism was coded in 632 admissions; Staphylococcus aureus was most common (57%), followed by the viridans group of streptococci (20%). Preexisting heart disease was present in 662 patients admitted (42%), among whom 81% had congenital heart disease, 8% had prosthetic valve endocarditis, and 5% had rheumatic heart disease. In-hospital mortality occurred in 84 patients (5%), 38 with preexisting heart disease. Death occurred in 12 of 25 patients (48%) with tetralogy of Fallot and pulmonary atresia, and 4 of 54 (8%) with prosthetic valve endocarditis. Among 46 deaths without preexisting heart disease, S aureus was the causative organism in 13 of 14 patients (93%) beyond infancy; among 32 infants who died, 10 (31%) were premature. CONCLUSIONS: In 2000 and 2003, we found a continuing shift in the epidemiology of pediatric infective endocarditis toward a higher proportion of children without preexisting heart disease. Risk factors for mortality included some forms of congenital heart disease and, among patients without preexisting heart disease, premature/neonatal age and S aureus as an etiologic agent.