Forty-eight cases of infective endocarditis (IE) that occurred in 42 patients with congenital heart disease were reviewed from 1970 through 1990 and were compared with a 20-year review of 108 cases diagnosed between 1953 and 1972. The review demonstrates that the natural history of IE in children has changed over the last 2 decades, with half of the cases occurring after surgery for congenital heart disease. In the postoperative group, 46% of patients had undergone valve replacement and 7 of these (29%) had a right ventricular to pulmonary artery valved conduit as the site for IE, suggesting significant additional risk in this setting. Among patients with nonsurgically treated congenital heart disease and IE, mitral valve prolapse has emerged as an important underlying heart lesion occurring in 29% of patients. The bacterial spectrum has shifted, with a significant increase in the incidence of uncommon causative organisms. Mortality has continued to decline with survivorship of 90% in this series.