AbstractBackgroundA history of congenital heart disease and previous transplantation are each independently associated with worse survival following pediatric heart transplantation. This study aimed to evaluate the characteristics and outcomes of children undergoing repeat heart transplantation in the United States based on the underlying diagnosis.MethodsThe United Network for Organ Sharing database was used to identify 8111 patients aged <18 years undergoing isolated heart transplantation from 2000 to 2021, including 435 (5.4%) repeat transplants. Restricted cubic spline analysis assessed the non‐linear relationship between inter‐transplant interval and the primary outcome of all‐cause mortality or re‐transplantation. Multivariable Cox regression assessed the impact of re‐transplantation on the primary outcome. Median follow‐up was 5.0 (interquartile range 1.9–9.9) years.ResultsRepeat transplant patients were older (median age 12 vs. 4 years; p < .001), and less likely to be in UNOS status 1A (66.0%, n = 287 vs. 81.0% n = 6217; p < .001) than primary transplant patients. Freedom from the primary outcome was 51.4% (95% confidence interval [CI] 45.5–57.2) among repeat transplants and 70.5% (95% CI 69.2–71.8) among primary transplants at 10 years (p < .001). Among repeat transplant patients, the relative hazard of the primary outcome became non‐significant when the inter‐transplant interval >3.6 years. Congenital heart disease was an independent predictor of mortality among primary (HR 1.8, 95% CI 1.6–1.9) but not repeat transplant (HR 1.1, 95% CI .8–1.6) patients.ConclusionsLong‐term outcomes remain poor for patients undergoing repeat heart transplantation, particularly those with an inter‐transplant interval <3.6 years. Underlying diagnosis does not impact outcomes after repeat transplantation, after accounting for other risk factors.