Orthodeoxia is a rare clinical syndrome characterized by deoxygenation in the upright position and relieved by recumbency. Our rounds illustrate how cardiovascular imaging and echocardiography can be used to diagnose the etiology of this syndrome with respect to its association with patent foramen ovale (PFO) and ascending aortic aneurysms. The rounds also demonstrate the use of peri-operative transesophageal echocardiography (TEE) in understanding the mechanisms contributing to the condition and aid in appropriately planning medical and surgical management.