Atrial septal defect (ASD) is one of the most common congenital cardiac anomalies found in the adult population. Although usually asymptomatic in childhood, ASD will be symptomatic in approximately 75 percent of adults. The most common symptoms include fatigue, dyspnea on exertion, and palpitations. However, the presentation of ASD can be protean. We present four patients with secundum ASD with unusual clinical manifestations. Patient 1 had moderately severe mitral regurgitation. Patient 2 had pulmonary edema with generalized left ventricular impairment. Patient 3 had chest pain typical of angina pectoris. Patient 4 had right-to-left shunt following an orthopedic surgical procedure. These patients had chest radiographs and electrocardiograms typical of secundum ASD, but their presentations were uncommon. In three of four of these patients, dramatic resolution of symptoms followed surgical repair of their ASD.