Abstract: Objective  To investigate the safety and efficacy of nafamostat mesylate in hemodialysis (HD) patients with high bleeding risk.   Methods   A total of 60 patients with high bleeding risk undergoing HD treated in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2023 to August 2023 were randomly divided into anticoagulant group (nafamostat mesylate group) and no anticoagulant group, with 30 cases in each group. The efficacy and safety of HD were compared between the two groups.  Results  In the anticoagulant group, the use time of cardiopulmonary bypass pipeline was longer (t=5.118, P＜0.001), the average service life of dialyzer was longer (t=4.691, P＜0.001), the number of venous pressure alarm intervention was less (χ2=4.691, P＜0.010), the effective rate of grade 0-1 anticoagulation was higher (χ2=24.300, P＜0.001), the single chamber model urea clearance index (spkt/v) was higher (t=17.456, P＜0.010), and no transmembrane pressure alarm intervention and dialyzer replacement happened. In the anticoagulant group, the activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT), international normalized ratio (INR), fibrinogen (FG) and fibrin degradation products (FDP) had no significant differences in the samples from blood pipeline before heparin pump (blood collection point A) before HD, during HD at 1h, 2h, 3h, and end of HD, and in the sample from contralateral limb without autologous arteriovenous fistula (blood collection point C) after HD for 15min (F= 0.132, 1.708, 0.025, 1.394, 0.849 and 0.993 respectively; P=0.985, 0.135, 1.000, 0.229, 1.106 and 0.424 respectively). The activated clotting time (ACT) showed no significant difference in the samples from the blood pipeline behind the dialyzer (blood collection point B) during HD at 1h, 2h, 3h, and end of HD (F=0.297, P=0.914). No adverse events including allergic reaction, hyperkalemia, bleeding, arrhythmia occurred in the two groups.   Conclusion   Nafamostat mesylate has better efficacy and safety used as an anticoagulant for HD in patients with high bleeding risk.

Key words: Hemodialysis, Nafamostat mesylat, Anticoagulation