The purpose of this study was to create national estimates for the incidence of pediatric infective endocarditis (IE) in the United States and to determine if these changed after the implementation of the 2007 American Heart Association IE guidelines. It also sought to determine the effect of congenital heart disease (CHD) status on outcomes in IE. Hospital discharges with the diagnosis of IE in patients < 18 years old from the Kids’ Inpatient Database were identified from the years 2000, 2003, 2006, 2009, and 2012. Discharges were grouped into Pre- and Post-2007 groups to facilitate analysis surrounding the implementation of the guidelines in 2007. Patients were categorized by age, underlying CHD, and etiologic organism. Descriptive comparisons and changes in categorical variables were made between groups. Average annual IE hospitalization rates before and after the 2007 guidelines were 10.8 and 9.3 per 1,000,000 children, respectively. The proportion of IE patients with CHD was stable between time periods, (45% vs. 47%, p = 0.50). Mortality was higher in the Post-2007 time period for CHD patients than non-CHD patients (11.1% vs. 2.4%, respectively; p < 0.001), while there was no difference noted during the Pre-2007 time period (6.5% vs. 6.6%, respectively; p = 0.95). Streptococcus was more common among CHD patients than non-CHD patients (27% vs. 17%), while Staphylococcus was more common among non-CHD patients than CHD patients (34% vs. 24%, p < 0.001). Even though the incidence of IE was stable over time, mortality was higher in CHD patients after the implementation of the 2007 AHA IE prophylaxis guidelines.