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It is unclear whether cyclosporine A (CsA) can be withdrawn safely during follow-up after pediatric liver transplantation. In our transplant program we have been using a strict protocol to withdraw CsA. The aim of this study was to retrospectively assess the effects of CsA withdrawal after pediatric liver transplantation on the incidence of rejection and renal function. Between 1986 and 2001, 91 children received CsA for at least 2 yr after liver transplantation. Specific criteria for eligibility to withdraw CsA were set. In 53 of the 91 children CsA was withdrawn. In 35 patients (66%) withdrawal of CsA did not cause rejection. In these patients the renal function improved compared with baseline values (glomerular filtration rate (GFR) at 1 yr, +16 mL/minute/1.73 m3, P < 0.001; at 2 yr, +10 mL/minute/1.73 m3, P < 0.05). After CsA withdrawal, 18 patients developed rejection (34%), which could be effectively treated by methylprednisolone and restarting CsA. Failure to withdraw CsA was not associated with increased incidence of graft loss. A body weight below 10 kg at the time of transplantation correlated significantly with successful withdrawal of CsA (<10 kg, 85% vs. > 10 kg, 60%; P < 0.05). In conclusion CsA can successfully be withdrawn in a major proportion of selected pediatric liver transplantation patients during follow-up. The success rate is the highest in children with a body weight below 10 kg at the time of transplantation. Successful withdrawal improves renal function, whereas failure to withdraw is not associated with graft loss or persisting morbidity., (Copyright 2006 AASLD)