We describe an unusual case of orthodeoxia platypnea syndrome exacerbated by right ventricular inflow obstruction due to iatrogenic steroid-induced adipose deposition in cardiac tissues. A 68-year-old man on long-term prednisone therapy for eosinophilic pneumonia presented with progressive dyspnea worsened by bending forward. By using pulse oximetry, he was noted to have positional hypoxemia. Transthoracic echocardiogram demonstrated normal right-sided pressures but severe right to left shunting through a patent foramen ovale. Transesophageal echocardiogram showed a large patent foramen ovale, severe lipomatous hypertrophy of the interatrial septum, and massive adipose deposition in the pericardium causing compression of the right ventricular inflow tract. The patient underwent percutaneous closure of the patent foramen ovale, which resulted in the resolution of symptoms and hypoxemia. This case is unique because long-term steroid use resulted in reverse Lutembacher physiology and clinical orthodeoxia platypnea syndrome by inducing lipomatous hypertrophy of the interatrial septum and compression of the right atrium.