One of the most common causes of early graft failure in children undergoing renal transplantation is vascular thrombosis. Numerous risk factors for graft thrombosis have been previously described. Children with various types of thrombophilias such as protein C, protein S and factor V Leiden deficiencies are at an increased risk for vascular thrombosis. Infants and small children with these disorders undergoing renal transplantation have not been well documented in the literature. We reviewed our experience in the diagnosis, peri-operative management and follow up of these patients at our institution. A retrospective analysis of all children undergoing renal transplantation at our institution, using data obtained from the Pediatric Transplant Registry at our institution since May 2000 was performed. The indications for renal transplant included focal segmental glomerulosclerosis, renal dysplasia and reflux nephropathy. One patient had factor V Leiden mutation and two patients had protein S deficiency. Patients were anticoagulated in the peri-operative and post-transplant period. All index transplants were performed with living donor kidneys. There were no adverse outcomes in children with thrombophilias despite having significantly lower weight at the time of transplant vs. children without thrombophilia. The incidence of graft thrombosis in the pediatric renal transplant recipients is high. We identify a potential cause of thrombosis in children not well documented in the literature. A high index of suspicion combined with preoperative screening and diagnosis of thrombophilias and an appropriate treatment plan may decrease the incidence of graft thrombosis in infants and small children undergoing renal transplantation.