Excluding the left atrial appendage in patients with nonvalvular atrial fibrillation is a mechanical way to decrease stroke risk. During endothelialization, the closure device is exposed to circulating blood, which might activate the coagulation cascade. In excessive proportions, possibly resulting in the development of device-related thrombus, requiring a bridging period with optimal antithrombotic treatment. Initial protocol treatment is less suitable for patients with contraindications to anticoagulation. Less intensive antithrombotic regimens investigated suggest safety and efficacy, however further research is required. A tailored treatment, considering bleeding and thromboembolic risk based on patient/procedural characteristics in every patient, is probably the best approach.