The Watchman FLX device (Boston Scientific, Marlborough, MA) is indicated to reduce the risk of atrial fibrillation-related stroke in patients with an appropriate rationale for seeking an alternative to anticoagulation. However, anticoagulation has remained the first-line therapy. The manufacturer-sponsored CHAMPION-AF trial seeks to challenge this dogma. CHAMPION-AF will enroll 3000 subjects with CHA2DS2-VASc scores > 2 and without contraindications to anticoagulation at up to 150 sites. Subjects will be randomized 1:1 to left atrial appendage occlusion (LAAO) with the Watchman FLX device or a direct oral anticoagulant (DOAC). Patients will be followed for 36 months for a primary effectiveness composite endpoint of thromboembolic events and cardiovascular death as well as a primary safety endpoint of non-procedural bleeding. Abbott is conducting a similar trial of the Amulet device called CATALYST.