The database of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) was examined to identify factors that contribute to the poor transplant outcome rate seen in patients with Congenital Nephrotic Syndrome (CNS) (1). Between January 1, 1987 and January, 1997, 132 transplant recipients with the primary diagnosis of CNS were registered. Analysis of the index renal transplants for 78 living donor transplants (LDTx) and 54 cadaver transplants (CADTx) revealed a graft failure rate of 20.5% and 50.0%, respectively. A proportional hazards regression analysis of the CNS patients indicated that cadaver donor source (relative risk increase of 3.9, p<0.001) and recipient age less than 2 years of age (relative risk increase of 2.6, p=0.002) were simultaneous significant predictors of poor graft survival. Patients with CNS demonstrated decreased graft survival compared to the remainder of the registry adjusted for age and donor source (p=0.04). Graft failures were attributed to vascular thrombosis (26%), patient death with functioning graft (23%), chronic rejection (21%) and acute rejection (19%). Graft failure attributed to thrombosis occurred more frequently in CNS patients than in patients with other primary diseases (8.3% vs. 2.9%, p=0.002). Graft failure due to patient death with a functioning graft also occurred more frequently in CNS patients than in patients with other primary diseases (7.5% vs. 2.6%, p<0.003). Infections were the causes of death in 50% (5 of 10) of CNS patients with a functioning graft. Infection as a cause of death with functioning grafts was significantly greater in CNS patients (3.8%) than the rest of the registry (0.8%, p<0.006). We conclude that there is a high rate of renal graft failure in pediatric patients with CNS. Vascular thrombosis and death with a functioning graft were more frequent in patients with CNS compared to patients with other primary diseases. Care should be taken to eliminate risk factors for hypercoagulability and infections prior to transplantation in children with CNS.