Platypnea-orthodeoxia is a peculiar syndrome characterized by a right-to-left shunt, which occurs in the upright position. The diagnosis is made by contrast transesophageal echocardiography, paying attention to include contrast visualization in the orthostatic decubitus. The association of this syndrome with a fenestrated atrial septal aneurysm is rare and probably underlies a peculiar and also rare mechanism of shunting in presence of normal pulmonary pressure. We report of a case of a 58-year-old man with a fenestrated atrial septal aneurysm and platypnea-orthodeoxia syndrome treated by surgical closure of the atrial defect.