Nafamostat mesilate is a prostacyclin analog inhibiting serine proteases and has been widely used as an anticoagulant in hemodialysis because of its pharmacological advantages, one of which is to reduce bleeding tendency. There have been a few case reports of allergic reactions by nafamostat mesilate in Japan, and only one case report of anaphylaxis in Korea. Here, we report two cases of patients showing anaphylaxis induced by nafamostat mesilate. The first case is a 78-year old female consulted to our clinic for the evaluation of possible causes of cardiac arrest during dialysis. Nafamostat mesilate was used as an anticoagulant for hemodialysis to minimize the risk of bleeding as she had undergone bursa excision and wound closure due to infective bursitis of her ankle. On the sixth session of hemodialysis after surgery, she had sudden cardiac arrest following complaining itching sense and urticaria on her thighs and abdomen. After successful resuscitation, she had been treated in the intensive care unit for 5 days. The second case is a 66-year old female consulted to our clinic due to dyspnea, cough, and itchy sense with nafamostat mesilate. As both patients complained mild allergic symptoms including itchy sense, and urticaria during the previous dialysis, we suspected allergic reaction. We performed skin test and basophil activation test using nafamostate mesilate on the patients. The intradermal tests showed positive results in both patients, and basophils of the patients treated with nafamostat mesilate were found to have significant upregulations in both CD63 and CD230c expression. They restarted hemodialysis using heparin instead of nafamostat mesilate and they did not have any adverse reactions. In conclusion, nafamostate mesilate should be considered one potential cause of cardiac arrest or allergic reactions during dialysis, although an allergic reaction to nafamostat mesilate is rare, and it is very important to have a clinical suspicion during diagnosing hypersensitivity to nafamostat mesilate.