Introduction: The aim of the present retrospective study is to evaluate the long term safety of radiotherapy (Rt) in orthotopic liver transplanted (OLT) children, in the eventuality that this technique might be applied to promote liver cell engraftment as shown in liver cell transplantation (LCT) in animal models. Methods: Between 1986 and 1990, Rt has been used to control rejection in 14 OLT children, amongst a cohort of 136 children transplanted during the same period. Rt was administered three consecutive days, at a dose of 150 centigray directed to the liver. All children at that time were under triple immunosuppression, Cyclosporin, Azathioprine & Prednisone. 13 of 14 had received one or more course of OKT3 to control rejection, and 11 had also received anti thymocyte globulins (ATG). Rt was a rescue treatment after failure to control rejection. Results: Full rejection control was achieved in 6 patients and partial control in 2. All 8 are alive at the 2003 follow up, one suffering from chronic hepatitis C. One had experienced acute limited adenovirus infection, and one had received chemotherapy for EBV related Hodgkin’s disease 96 months after Rt. Patients with partial control of rejection were later switched to FK506. 2 of 14 patients with ongoing rejection received additional OKT3, were switched to FK506 and are currently alive and well. 4 died from adenovirus fulminant hepatitis (n=1) (OKT3 related), autoimmune hepatitis recurrence (n=1), and re-transplantation (n=2). Survival in the Rt group was 71.5% and in the control group 73%, within the range of transplantation survival at that time. Respective incidence of Post-Transplant Lymphoproliferative Disease was 1/14 versus 4/122, adenovirus hepatitis 2/14 versus 3/122, de novo hepatitis C 1/14 versus 10 /122, and re-transplantation 3/14 versus 26/122. 10 of the 14 children had long term follow up biopsy, up to 152 months after Rt. 6 of 10 had no signs of Rt-induced related damage. 4 had mild to moderate fibrosis. The long term follow up biopsy in the control group showed mild to moderate fibrosis in 40/85 and severe fibrosis in 1/85. Conclusion: Because of the numerous treatment administered, it remains uncertain that radiotherapy played a role to control rejection. However, the present series show that no long term side effects of Rt were observed, and that complications in that group were not different no more frequent as compared to the series of children transplanted during the same period. Liver fibrosis, a possible side effect of Rt was no more frequent in these patients as in controls. Clinical use of Rt may be considered for LCT engraftment facilitation if further animal studies confirm the potential benefit of this treatment.