We describe a series of 11 high-risk neonates with infective endocarditis (IE) in this retrospective review. Previously IE has rarely been diagnosed in newborns and is usually fatal. The frequency was 4.3 cases per 100 patients. Five patients survived. Microorganisms included gram positives such as S. aureus and coagulase-negative Staphylococcus, gram negatives such as Klebsiella pneumoniae, Enterobacter cloacae, Enterococcus faecalis, Serratia marcescens, and Acinetobacter calcoaceticus. Echocardiographic location of the lesions showed four left sided, five right sided, and two bilateral. We conclude that IE may be more common than previously described. Prompt diagnosis and treatment led to survival in 45% of our patients. Prospective studies are needed to identify patients at risk and to establish the true incidence of IE in high-risk neonates.