AbstractAtrial fibrillation (AF), as the most common cardiac rhythm disturbance, gains in importance not only for the persons affected, but also for health care and social economy due to thromboembolic events, of which stroke is the most serious, disabling, and life threatening one. Cardiac embolism is due to thrombus formation mainly in the left atrial appendage (LAA). The pathophysiology leading to increased thrombogenicity is complex and requires a remodelling of the LAA structure, decreased LAA blood flow, activation of inflammatory processes, deviations of the hemostatic/fibrinolytic system, and activation/dysfunction of endothelial/endocardial cells. Altogether, a prothrombotic state proposed by Virchow more than 150 years ago. The presence of a LAA thrombus, therefore, is a result of a dynamic process of clot formation and lysis. A comprehensive understanding of this pathophysiology is helpful to optimize the management of patients at high risk of cardioembolic stroke. Especially those with contraindications for oral anticoagulation are in a need of an alternative approach that is not associated with a long-term risk of hemorrhage and other attendant circumstances. The reasonable alternative may be the exclusion of the LAA cavity from circulation by either surgical or percutaneous catheter-based procedures.