<h3>Purpose</h3> National data on the efficacy of re-transplantation in children, in whom waitlist mortality approaches 20%, is scarce. <h3>Methods</h3> The United Network for Organ Sharing (UNOS) Database was used to identify 6,244 patients aged <18 years undergoing isolated heart transplant from 2004-2021, including 5,913 (94.7%) primary transplants and 331 (5.3%) re-transplants. The primary outcome was all-cause mortality. Multivariable cox regression was used to assess the impact of re-transplantation on survival, adjusting for patient, donor and hospital characteristics. Median follow-up was 4.5 (range 0.0-16.2) years. <h3>Results</h3> Re-transplant patients were older (median age 12 vs 4 years; p<0.01), more likely to be female (54.1%, n=179 vs 44.1%, n=2609; p<0.01), and less likely to be in UNOS status 1A (67.7%, n=224 vs 83.4% n=4932; p<0.01) than those undergoing primary transplants. The main indication for re-transplantation was allograft vasculopathy (60.7% n=201), followed by chronic rejection (10.6%, n=35) and primary failure (8.8%, n=29). The overall 90-day survival was 94.8% (95% confidence interval (CI) 94.2-95.3), this was similar between the groups (p=0.28). The unadjusted 10-year survival was 48.4% (95% CI 41.2-55.7%) among re-transplants and 71.6% (95% CI 70.0-73.2%) among primary transplants (p<0.01) (Figure 1). Re-transplantation was an independent predictor of long-term mortality in multivariable analysis (hazard ratio (HR) 1.8, 95% CI 1.4-2.2), other predictors included earlier transplant year (HR 0.9, 95% CI 0.8-0.9 per 5-years). <h3>Conclusion</h3> Despite advancements in overall outcomes, late survival following pediatric heart re-transplantation is significantly worse than primary transplantation. Increased awareness, prevention, diagnosis and management of coronary disease in pediatric heart transplant patients may improve patient outcomes and organ stewardship.