Background. Atresia of the coronary sinus orifice with a persistent left superior vena cava is an intrinsically benign cardiac anomaly with important surgical implications. Methods. The medical records of 5 patients with atresia of the coronary sinus orifice with a persistent left superior vena cava were reviewed retrospectively, and a computer search of the world literature describing this cardiac malformation was undertaken. Results. The 5 patients ranged in age from 9 months to 5 years. In 2, the diagnosis was made preoperatively by angiocardiography, and in 3, the abnormality was found incidentally at the time of cardiotomy for repair of associated congenital heart disease. Four of the 5 patients underwent repair of associated cardiac lesions. During operation, care was taken to avoid disruption of left superior vena cava flow to prevent coronary venous obstruction. All patients survived and are doing well at follow-up. Conclusions. Atresia of the coronary sinus orifice with persistent left superior vena cava is, in itself, a benign anomaly without physiologic consequence. However, the recognition of this lesion during repair of associated cardiac lesions is of vital importance to the cardiac surgeon. Interruption of this sole route of coronary venous drainage can potentially lead to myocardial ischemia and necrosis.