Immunoglobulin mitigates autoimmune disease and facilitates acceptance of ABO-incompatible transplanted organs. To test the hypothesis that treatment with immunoglobulin is associated with improved graft survival and a decreased rate of allograft rejection, a cohort study of primary liver transplant recipients in the Studies of Pediatric Liver Transplantation registry was performed. The outcomes of 336 pediatric liver transplant recipients who received immunoglobulin within 7 days of liver transplantation were compared with the outcomes of 1612 recipients who did not receive immunoglobulin. The outcome measures were patient survival, death-free graft survival, and allograft rejection. The Kaplan-Meier probability of patient survival was not different between patients treated with immunoglobulin and patients who did not receive immunoglobulin. Death-free graft survival was increased in patients treated with immunoglobulin (hazard ratio of death-free survival = 0.57, P = 0.014). The probability of allograft rejection at 3 months was 31% for patients treated with immunoglobulin versus 40% for patients who did not receive immunoglobulin (hazard ratio = 0.81, P = 0.02). The proportion of patients with 2 or more episodes of allograft rejection was lower in patients treated with immunoglobulin (13.1% with immunoglobulin versus 19.2% with no immunoglobulin, P = 0.009). Treatment with immunoglobulin was associated with a decreased risk for allograft rejection, whereas use of cyclosporine as the initial immunosuppression and transplantation before 2002 were independently associated with an increased risk of allograft rejection in pediatric liver transplantation recipients. A trend toward a decreased rate of retransplantation was detected in the population that received treatment with immunoglobulin.