A new diagnostic schema for infective endocarditis (IE), the Duke criteria, has been compared with the previously published criteria of von Reyn in adult patients. This study was designed to analyze the clinical characteristics of a group of pediatric patients with IE and to compare the diagnostic efficiency of both sets of criteria. We reviewed retrospectively the clinical records of 38 patients, 22 with predisposing heart disease (Subgroup A) and 16 with no known cardiologic abnormality (Subgroup B). Ventricular septal defect was the most frequent preexisting heart disease (31.8%) and central venous catheters were the most frequent predisposing factor (68.7%). Comparison of the clinical features between subgroups (A vs. B) showed differences only for the presence of a new regurgitant murmur (9% vs. 44%, P < 0.05) and a hemoglobin value ≤10 g/dl (50% vs. 94%, P < 0.05). The most frequent microorganisms isolated were viridans streptococci (36%) in Subgroup A and Staphylococcus aureus (50%) in Subgroup B. Of the 6 pathologically confirmed cases all would have been classified as clinically definite by the Duke criteria, as compared with 2 of 6 being defined as probable and one being rejected by von Reyn criteria. Of the 32 cases clinically defined 19 (59%) were classified as definite by the Duke criteria, and 11 (34%) were probable by the von Reyn criteria (difference 25%, P < 0.01). Although no case of IE was rejected by Duke criteria, 8 (25%) were rejected by von Reyn criteria (difference 25%, P < 0.01), with all 8 classified as possible by Duke criteria. We conclude that the Duke criteria were superior to the von Reyn criteria for the diagnosis of pediatric IE, including more cases as definite and significantly fewer cases as rejected.