It is important to prevent on-device thrombus formation without increasing the risk for bleeding complications after successful interventional left atrial appendage closure. Therefore, choosing the optimal antithrombotic therapy poses a challenging task. While major clinical studies investigated patients eligible for oral anticoagulation using vitamin K antagonists, the vast majority of implants in ‘real life’ are performed in patients with contraindications to oral anticoagulation after serious bleeding events. In this patient population, strategies using dual antiplatelet therapy were found to be a sound alternative; however, the optimal duration of antithrombotic therapy remains unclear. Future studies will have to investigate the role of direct anticoagulants for post-implant thrombus formation and address the question of whether left atrial appendage closure obviates the need for long-term aspirin therapy.