Objective: Orthotopic heart transplantation is considered a rescue option for children with failing staged palliation or repair of hypoplastic left heart syndrome. We present our strategy for management, and outcomes, for these complex patients. Methods: We transplanted 68 consecutive children, with diagnoses of hypoplastic left heart syndrome in 31, cardiomyopathy in 20, and post-operative complex congenital heart disease in 17. Of these patients, 9 (13.2%) were neonates, and 46 (67.6%) were infants. Median age was 118.5 days. Operative technique involves bicaval cannulation and anastamoses with continuous low flow bypass, and either short periods of circulatory arrest or continuous low flow antegrade cerebral perfusion for reconstruction of the aortic arch. Initial reperfusion of the donor heart utilizes glutamate and aspartate substrate enriched white blood cell filtered cardioplegia. Immunosuppressive therapy includes induction (pulse steroids, gamma globulin, and polyclonal rabbit antithymocyte globulin) and initial maintenance (calcineurin inhibitor, an anti-proliferative agent, and a weaning steroid protocol). Of the 31 patients with hypoplastic left heart syndrome, 23 underwent primary transplantation, and 8 underwent rescue transplantation from failing staged palliation in seven, or attempted biventricular repair in one. Of the seven patients who had failing staged palliation, three had undergone only the Norwood Stage 1 operation, 2 had undergone a Norwood Stage 1 operation and a Glenn superior cavopulmonary anastomosis and two had undergone a Norwood Stage 1 operation, a Glenn superior cavopulmonary anastomosis, and a completion Fontan operation. Results: The group undergoing primary transplantation was younger (p equals 0.007), weighed less (p equals 0.003), and waited longer for an appropriate donor heart (p equals 0.021) compared to those requiring rescue transplantation. No significant difference exists between the groups with regards to donor heart ischaemic time or post-transplant length of hospital stay. Thirty day survival (p equals 0.156) and overall survival (p equals 0.053) was better in those having primary transplantation, although these differences were not statistically significant when a p value of less than 0.05 is considered to be significant. In those having primary transplantation, no patients had elevated panel reactive antibody greater than 10%. Half of the 8 requiring rescue transplantation had panel reactive antibody greater than 10%, and this subgroup did especially poorly. Conclusion: Cardiac transplantation can offer children with failing staged palliation their only chance of survival. Transplantation, however, carries a high risk in this subgroup, especially in the setting of elevated panel reactive antibody.