Platypnea-orthodeoxia syndrome is a rare disorder characterized by dyspnea and oxygen desaturation in upright position, with improvement of symptoms and blood oxygenation in supine position. Basically a right-to-left shunt (intracardiac or pulmonary) or a ventilation/perfusion mismatch are necessary to develop platypnea-orthodeoxia syndrome. Atrial septal defects, including patent foramen ovale (PFO), are known to be a frequent cause of platypnea-orthodeoxia syndrome. We describe herein the case of a 79-year-old woman with platypnea-orthodeoxia syndrome and PFO who developed a refractory worsening respiratory failure. Only the "rescue" emergency closure of PFO allowed the patient a clinical turning point with immediate and sustained respiratory improvement.