Platypnea-orthodeoxia is a rare syndrome characterized by dyspnea and hypoxemia that is exacerbated by assuming an upright position. The most common cause is intracardiac shunting through an atrial septal defect or patent foramen ovale (PFO). We present a 63-year-old man with dyspnea after right pneumonectomy for lung cancer, who was found to have a large PFO with right-to-left shunt in the presence of normal right-sided pressures. Percutaneous closure of the PFO led to resolution of symptoms.