Background The pediatric heart transplant literature contains little information regarding extracorporeal photopheresis (ECP), despite International Society for Heart and Lung Transplantation guidelines recommending it for recurrent/recalcitrant rejection. We report our experience with ECP in pediatric heart transplantation. Methods Data were obtained on heart transplant patients who were aged ≤ 18 years at the time of transplantation and received ECP between 1990 and 2012 at our institution. Results Twenty heart transplant patients underwent 22 courses of ECP. Median ages were 12.7 years (range, 0.3-18.5 years) at transplant and 15.3 years (range, 7.3-31 years) at initial ECP. Median time from transplant to ECP was 1.4 years (range, 0.1-12.6 years). The median ECP duration was 5.8 months (range, 1.9-16.1 months). Indications for ECP included rejection with hemodynamic compromise (HC) in 4 patients, rejection without HC in 12, and prophylaxis in 2. Eleven patients died at a median time of 3.1 years after the start of ECP. Survival after ECP was 84% at 1 year and 53% at 3 years. Eleven patients were considered non-compliant and had a trend toward lower survival of 75% at 1 year and 18% at 3 years (p = 0.06 compared with compliant patients). One patient developed Pneumocystis carinii pneumonia during ECP and post-transplant lymphoproliferative disease 21 months after finishing ECP. No other adverse effects or infectious complications associated with ECP were noted. Conclusions This case series represents the largest reported experience with ECP in pediatric heart transplantation. ECP can be safely applied in this patient group. Despite EPC, non-compliant patients showed a trend toward lower survival than compliant patients. © 2014 International Society for Heart and Lung Transplantation.