Abstract: OBJECTIVE To explore the clinical efficacy of fibrin adhesive and esomeprazole sodium in the treatment of peptic ulcer bleeding. METHODS From October 2015 to October 2018, 78 patients admitted to Hainan General Hospital for treatment of peptic ulcer bleeding were divided into control group 36 cases and experimental group 42 cases according to the treatment method. The control group was treated with fibrin adhesive under gastroscope to stop bleeding, and the experimental group was treated with fibrin adhesive combined with esomeprazole sodium. The efficacy of the two groups including the success rate of hemostasis, rebleeding rate, etc. was observed; the incidence of adverse reactions in the two groups during the treatment was observed. RESULTS The success rate of hemostasis in the control group was 100%, and that in the experimental group was 97.5%. The 24 h rebleeding rate of the control group was 11.1%, the 24 h rebleeding rate of the experimental group was 2.6%; the 168 h rebleeding rate of the control group was 11.1%, and the 168 h rebleeding rate of the experimental group was 0.0%. The increasing trend of hemoglobin level in the control group after treatment was weaker than that of the experimental group; the decreasing trend of the gastrointestinal symptoms score of the control group after treatment was weaker than that of the experimental group, the ulcer area of the control group was larger than that of the experimental group, and Rockall score was higher than that of the experimental group. The incidence of hematemesis and melena after treatment in the control group was higher than that in the experimental group. CONCLUSION Fibrin adhesive combined with esomeprazole sodium in the treatment of peptic ulcer bleeding can effectively reduce the postoperative rebleeding rate of patients without causing serious adverse events, and can be promoted as a safe and effective treatment in the clinic.