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Atrial fibrillation (AF) is a major risk factor for ischemic stroke, accounting for more than 37 million cases worldwide. In AF, the left atrial appendage (LAA) is the most common site of thrombus formation, and its ligation/closure with the WATCHMAN device is a good alternative to long-term oral anticoagulation, especially in patients with contraindications to warfarin. However, the implantation procedure is associated with various risks and complications. A short-term anticoagulant and antithrombotic administration are essential after implantation. However, no consensus has been reached on the optimal regimen. The WATCHMAN device is non-inferior to warfarin and is a safe alternative for the prevention of stroke and systemic embolization related to non-valvular atrial fibrillation (NVAF). Important procedure-related complications include pericardial effusion (PE), device embolization, procedure-related ischemic stroke, and device-related thrombosis (DRT) formation. It is essential to optimize post-implantation therapy according to individual patient bleeding risk, DRT formation, and contraindication to direct oral anticoagulants (DOACs). Recent studies have also shown that DOACs are a convenient and non-inferior substitute for warfarin. Furthermore, patients with absolute contraindications to OACs/DOACs can only be managed with dual antiplatelet therapy (DAPT). Transesophageal echocardiography (TEE) should be used to assess residual peridevice flow and possible DRT formation at days 45 and 12 months. Low molecular weight heparin (LMWH) and OAC are excellent choices for DRT treatment if detected. This review summarizes the most important complications of the WATCHMAN device in the existing literature and discusses various anticoagulation strategies and challenges post-implementation.