During the pandemic of the new coronavirus infection, there is increasing evidence of neurological complications associated with COVID-19. There is no doubt that stroke can be a major complication in patients with severe disease course.Objective: to determine the safest and most effective anticoagulant for stroke prevention in patients with severe COVID-19.Patients and methods. A prospective study enrolled 520 patients with severe COVID-19. We used the following criteria for severe COVID-19: SpO2 <92% on room air at sea level, PaO2 /FiO2 <300 mm Hg, respiratory rate >30 breaths/min, lung infiltrates >50% on computed tomography. The study included 509 patients, divided into three groups depending on the type of anticoagulant therapy: patients of the 1st group received 24–36 thousand IU of heparin, patients of the 2nd group – enoxaparin at a dose of 1 mg/kg per day, patients of the 3rd group – rivaroxaban at a dose of 20 mg/day. The duration of anticoagulant administration depended on the severity of the patient's condition, dynamics of laboratory parameters (D-dimer, fibrinogen, international normalized ratio, activated partial thromboplastin time, platelet count), and varied from 2 to 6 weeks. In addition, we studied the incidence of ischemic and hemorrhagic strokes and transient ischemic attacks during a 6-week follow-up period. The article also presents a clinical case of large artery thrombosis in a young patient with severe COVID-19 without stroke risk factors.Results and discussion. Even against the background of active primary prevention, stroke incidence was 2.6% (0.6% for ischemic stroke, 1.4% for venous stroke, and 0.6% for hemorrhagic stroke). The highest stroke incidence was observed in the group of patients receiving heparin. In contrast, the prevention of thrombotic complications in patients receiving low-molecular-weight anticoagulants or rivaroxaban showed the best results with minimal morbidity and mortality in severe COVID-19.Conclusion. Stroke can be a complication of COVID-19, and preventive anticoagulant therapy using low-molecular-weight heparin or a factor X inhibitor effectively prevents this complication.