AbstractGiven an increased risk of both thrombosis and bleeding, thrombotic thrombocytopenic purpura (TTP) presents a unique challenge when anticoagulation is required for comorbid disease, particularly in the setting of major bleeding events. We present for the first time a patient with TTP and atrial fibrillation, presenting with recurrent stroke, but unable to tolerate anticoagulation due to prior intra‐cerebral hemorrhage. To address both issues concomitantly, we describe the successful application of a novel management approach to facilitate left atrial appendage occlusion, there by offering a non‐pharmacologic means of stroke prevention without added bleeding risk.