Abstract Background/Introduction The management of heart failure (HF), particularly in the context of reduced ejection fraction, is further complicated by an increased risk of thromboembolic events. Structural alterations of both left ventricle and mitral valve contribute to mitral regurgitation (MR). However, the body of evidence provides inconclusive insights into the relationship between MR and thromboembolic risk. Purpose This study aimed to investigate the impact of transcatheter edge-to-edge repair (TEER) on thrombin generation, clot permeation and clot lysis time in HF patients with severe MR eligible for mitral TEER. Methods A cohort of 31 HF patients with severe MR undergoing TEER underwent systematic evaluation at three time points. Coagulation parameters, including fibrinogen concentration, thrombin generation, fibrin clot permeability (Ks), and clot lysis time (CLT), were assessed. Comprehensive evaluations also covered echocardiographic, laboratory, and clinical parameters. Results TEER induced changes in fibrinogen levels (p=0.009, visit 3 vs. visit 2) and improved fibrin clot properties over a 50-day follow-up (Ks, p=0.005, visit 3 vs. visit 2). No significant differences were observed among time points in analyzed blood clot parameters. Linear regression, incorporating thrombin generation variables, Ks, and CLT for delta NT-proBNP, highlighted CLT as the sole predictor of NT-proBNP change between visit 2 and visit 1 (p=0.03; R2=0.18). Conclusions MR reduction through TEER led to transient alterations in fibrinogen concentration and improved fibrin clot characteristics. Additionally, baseline CLT emerged as a significant predictor of early NT-proBNP reduction, emphasizing its role as a key indicator of the hemodynamic response to TEER.