Introduction. Every year there is more and more data on the gender characteristics of cardiovascular diseases and factors predisposing to their development. It is now well known that men and women with atrial fibrillation (AF) differ in most clinical and demographic characteristics. The most formidable complication of atrial fibrillation is thromboembolic syndrome, which develops in 8-15% of cases. The system of signaling molecules CD40-CD40L is involved in the processes of thrombosis and inflammation. The main source of soluble CD40L is activated platelets. In this regard, it seems relevant to us to analyze the CD40/CD40L system in patients with AF of different sexes. Purpose: to study the content of CD40 and soluble CD40 ligand in blood serum in patients with non-valvular atrial fibrillation of different sexes, receiving anticoagulant therapy and having a history of TO and patients without thrombotic complications. Materials and Methods: The study included 22 healthy volunteers (11 women and 11 men) and 60 patients over 18 years of age with a diagnosis of atrial fibrillation (mean age 56.6±17.9), verified on the basis of clinical guidelines (ESC 2020 recommendations on diagnosis and treatment of atrial fibrillation), confirmed by ECG, receiving anticoagulant therapy in accordance with current recommendations. Of these, 21 patients developed thrombotic complications on the background of adequate anticoagulant therapy. Two groups of patients were formed: the group without thrombotic complications consisted of 18 women and 21 men, and the group of patients with thrombotic complications that occurred consisted of 10 women and 11 men. The study of the content of CD40 (pg/ml) and sCD40L (ng/ml) in blood serum was carried out by enzyme immunoassay. Results: an increased content of sCD40L was found in women compared with men in the group of patients with TO Me-17.98(14.71;19.58) vs 14.07(9.83;17.95) and in the group without TO Me-15.58(10.82;19.21) vs 9.58(6.19;15.14) p≤0.005; no differences were found in the group of healthy volunteers. There was no statistically significant difference in CD40 levels between men and women in the groups of patients with AF. Conclusion: thus, a comparative analysis of the indicators of the CD40/sCD40L system demonstrated significant gender differences in patients with AF. Thus, women were characterized by higher levels of the thrombus marker sCD40L compared to men, the highest level was observed in women in the group with thrombotic complications.