Total anomalous pulmonary venous return is a rare disorder characterized by the lack of direct connection of the pulmonary veins to the left atrium; instead, the pulmonary veins connect either directly to the right atrium or indirectly via a vein connected to the right atrium. This results in oxygenated blood ultimately draining into the right atrium and mixing with deoxygenated blood, necessitating a right-to-left atrial shunt to survive. Although it can be an isolated defect, in approximately two-thirds of cases total anomalous pulmonary venous return is associated with complex cardiac defects and frequently with heterotaxy syndrome, an embryologic disruption of right and left laterality of the thoracic and abdominal organs. Children with heterotaxy and total anomalous pulmonary venous return have even higher rates of early and late morbidity and mortality. This chapter details the perioperative management of a patient with recurrent pulmonary venous stenosis and intestinal malrotation requiring urgent abdominal surgery and outlines the appropriate management strategies for high-risk patients with this physiology.