Deep hypothermic circulatory arrest with cardiopulmonary bypass is indicated for complex surgical operations in adult patients involving the aortic arch, thoracoabdominal aorta, cerebral vasculature, and tumors extending into the vena cava and heart. Understanding the principles of ischemic-reperfusion injury and the effects of hypothermia in attenuating this process is fundamental to the delivery of effective postoperative care. Neurologic injury is the most troublesome adverse effect after the use of deep hypothermic circulatory arrest and cardiopulmonary bypass, presenting as either a transient neurologic deficit (5.9% to 28.1%) or an irreversible neurologic injury (1.8% to 13.6%). In patients with neurological injury, early postoperative mortality is markedly increased (18.2%), and for those patients that survive, long-term cognitive disability is still evident 6 months later. Early postoperative support of organ function, along with timely diagnosis and treatment of organ injury, is essential in minimizing perioperative morbidity, particularly neurologic morbidity. Meticulous management of fluids, maintaining stable cardiovascular hemodynamics with particular attention to systolic blood pressure, optimizing oxygen delivery, limiting ventilator-associated lung injury, intensive insulin therapy for control of blood glucose levels, and avoidance of hyperthermia are essential in limiting organ injury and reducing perioperative morbidity and mortality.