We describe 2 patients who experienced right-to-left shunting during support with a left ventricular assist device as a result of patent foramen ovale. In the first patient, the patent foramen ovale was not found until autopsy. In the second patient, fluctuations in continuous mixed venous oxygen saturations caused us to suspect a patent foramen ovale, which was confirmed with transesophageal contrast echocardiography. We promptly repaired the defect and this patient survived. When patients on assist devices experience unexplained arterial hypoxemia, a patent foramen ovale should be considered. If a patent foramen ovale is found, surgical correction should be done early.