Infants with an unbalanced atrioventricular septal defect (AVSD) frequently present with comorbidities that may have an impact on their medical course and outcome. This study aimed to assess outcomes and explore possible prognostic indicators for patients undergoing surgical palliation for an unbalanced AVSD. The medical records of all infants presenting to the authors' institution with an unbalanced AVSD over a 5-year period were retrospectively reviewed for assessment of outcomes and comorbidities. The study group consisted of 44 patients with an overall survival rate of 51% for the entire follow-up period. The majority of these patients (88%) underwent single-ventricle palliation, with an 83% rate of survival to initial hospital discharge and an overall long-term survival rate of 50%. The midterm outcome was significantly worse than that for a cohort of hypoplastic left heart syndrome patients undergoing single-ventricle palliation during the same period (P = 0.03). In addition, 30% of the patients required either repair or replacement of their systemic atrioventricular valve at initial palliation or during subsequent follow-up evaluation. Of the patients with an unbalanced AVSD, 75% had associated congenital anomalies. In conclusion, infants with an unbalanced AVSD are a high-risk population with diminished midterm survival compared with palliated patients who have more classic forms of hypoplastic heart syndromes. This may be due to the higher incidence of both severe atrioventricular valve regurgitation and important associated congenital anomalies.