Patent foramen ovale (PFO) may complicate left ventricular assist device (LVAD) therapy. We report a 70-year-old male with a HeartMate II LVAD at increased risk for thromboembolic stroke secondary to a PFO with right-to-left shunting and a large mobile thrombus on his right atrial pacing lead. Via percutaneous intervention, a 25 mm Cribiform Amplatzer atrial septal occluder was successfully deployed across the PFO without complications. This is the first reported case of percutaneous PFO closure to prevent paradoxical thromboembolism in a normoxic patient with an LVAD. In addition, arterial desaturation and the sequelae of chronic hypoxemia were prevented. Strategies to diagnose PFO at the time of LVAD implantation and physiological implications of a right-to-left atrial shunt during mechanical unloading of the failing left ventricle are reviewed.