Background. Rejection associated with heart failure or death occurs after pediatric cardiac transplantation but has had limited analysis.Methods. We analyzed the records of 96 consecutive pediatric cardiac transplant recipients who survived to hospital discharge.Results. Eighteen patients (19%) experienced 23 episodes of heart failure or death associated with rejection. Univariate analysis demonstrated black race (p = 0.041), transplantation after 12 months of age (p = 0.032), later time after transplantation (p = 0.037), rejection episode in the first year after transplantation (p = 0.001), and history of two or more rejection episodes (p < 0.001) were significantly associated with rejection seen with heart failure. A multivariate regression analysis identified two or more rejection episodes to be the only independent risk factor for the development of rejection with heart failure (odds ratio 20; 95% confidence limits, 4-104; p < 0.0001).Conclusions. This study identified pediatric heart transplant recipients with a history of previous rejection episodes to be at a higher risk for symptomatic or fatal rejection. Further studies are needed to determine if intensification of maintenance immunosuppression, long-term rejection surveillance, or both in patients with multiple rejection episodes could reduce morbidity and mortality from rejection. Copyright (C) 1999 The Society of Thoracic Surgeons.