An atrioventricular septal defect is a defect in the center of the heart consisting of a common atrioventricular valve, a primum atrial septal defect, and an inlet ventricular septal defect. When the common valve is not positioned equally over both ventricles it is called an unbalanced atrioventricular septal defect. This unbalance leads to a decreased inflow of blood to one of the ventricles, and that ventricle and outflow tract are often hypoplastic. The degree of unbalance can vary widely, ranging from mild, which in effect is similar to a large ventricular septal defect, to severe, which can often involve a hypoplastic ventricle and dependence on a patent ductus arteriosus to provide adequate flow to the affected circulation. This chapter discusses the anesthetic management of a 1-day-old patient with trisomy 21 and an unrepaired, unbalanced atrioventricular septal defect undergoing a laparoscopic repair of duodenal atresia. Anesthetic concerns regarding patients with trisomy 21, physiologic changes with laparoscopic surgery and implications of an unbalanced atrioventricular septal defect are all examined in detail.