Patients with a durable, continuous-flow left ventricular assist device (LVAD) are commonly prescribed the combination of an oral anticoagulant and an oral antiplatelet agent as prophylaxis against device thrombosis and systemic embolic events. Current International Society of Heart and Lung (ISHLT) guidelines recommend warfarin with an INR goal of 2–3 and concomitant aspirin 81–325 mg daily for patients with a HeartMate II LVAD. Unfortunately, gastrointestinal (GI) bleeding is very common in these patients because of multiple factors including the development of arteriovenous malformations and acquired von Willebrand syndrome. If this bleeding cannot be corrected through interventional measures, it then requires at least temporary, and potentially permanent, cessation of antiplatelet or anticoagulant therapy. Patients who continue to bleed while off all antithrombotic therapies present a clinical challenge. We describe the successful management of a patient with refractory GI bleeding through the use of inhaled desmopressin.