Background: Endomyocardial biopsy (EMB) is costly and discomforting yet remains a key component of surveillance after pediatric heart transplantation (HT). Donor‐derived cell‐free DNA (dd‐cfDNA) has been histologically validated with high negative predictive value, offering an alternative to surveillance EMB (sEMB). Methods: We implemented an alternative surveillance protocol using commercially available dd‐cfDNA assays in place of sEMB after pediatric HT. Recipients ≧7 months post‐HT with reassuring clinical assessment were referred for dd‐cfDNA. When not elevated above the manufacturers' threshold, sEMB was deferred. Subsequent clinical status and results of follow‐up EMB were analyzed. Results: Over 17 months, 58 recipients [34% female, median age at HT 3.1 years (IQR 0.6–10.6)] had dd‐cfDNA assessed per protocol. Median age was 14.8 years (8.4–18.3) and time from HT 6.0 years (2.2–11.2). Forty‐seven (81%) had non‐elevated dd‐cfDNA and 11 (19%) were elevated. During a median of 8.7 months (4.2–15), all are alive without allograft loss/new dysfunction. Among those with non‐elevated dd‐cfDNA, 24 (51%) had subsequent sEMB at 12.1 months (6.9–12.9) with 23 showing no acute rejection (AR): grade 0R/pAMR0 (n = 16); 1R(1A)/pAMR0 (n = 7). One had AR (grade 2R(3A)/pAMR0) on follow‐up sEMB after decreased immunosuppression following a diagnosis of PTLD. All 11 with elevated dd‐cfDNA had reflex EMB at 19 days (12–32) with AR in 4: grade 1R(1B‐2)/pAMR0 (n = 3); 1R(1B)/pAMR2 (n = 1). Conclusions: dd‐cfDNA assessment in place of selected, per‐protocol EMB decreased surveillance EMB by 81% in our pediatric HT recipient cohort with no short‐term adverse outcomes. Individual center approach to surveillance EMB will influence the utility of these findings. [ABSTRACT FROM AUTHOR]