AIM: To define the optimal injection volume of epineph-rine with high efficacy for hemostasis and low complication rate in patients with actively bleeding ulcers. METHODS: This prospective, randomized, comparative trial was conducted in a medical center. A total of 228 patients with actively bleeding ulcers (spurting or oozing) were randomly assigned to three groups with 20, 30 and 40 mL endoscopic injections of an 1:10000 solution of epinephrine. The hemostatic effects and clinical outcomes were compared between the three groups. RESULTS: There were no significant differences in all background variables between the three groups. Initial hemostasis was achieved in 97.4%, 98.7% and 100% of patients respectively in the 20, 30 and 40 mL epinephrine groups. There were no significant differences in the rate of initial hemostasis between the three groups. The rate of peptic ulcer perforation was significantly higher in the 40 mL epinephrine group than in the 20 and 30 mL epinephrine groups (P < 0.05). The rate of recurrent bleeding was significantly higher in the 20 mL epinephrine group (20.3%) than in the 30 (5.3%) and 40 mL (2.8 %) epinephrine groups (P < 0.01). There were no significant differences in the rates of surgical intervention, the amount of transfusion requirements, the days of hospitalization, the deaths from bleeding and 30 d mortality between the three groups. The number of patients who developed epigastric pain due to endoscopic injection, was significantly higher in the 40 mL epinephrine group (51/76) than in the 20 (2/76) and 30 mL (5/76) epinephrine groups (P < 0.001). Significant elevation of systolic blood pressure after endoscopic injection was observed in the 40 mL epinephrine group (P < 0.01). Significant decreasing and normalization of pulse rates after endoscopic injections were observed in the 20 mL and 30 mL epinephrine groups (P < 0.01). CONCLUSION: Injection of 30 mL diluted epinephrine (1:10000) can effectively prevent recurrent bleeding with a low rate of complications. The optimal injection volume of epinephrine for endoscopic treatment of an actively bleeding ulcer (spurting or oozing) is 30 mL. AIM: To define the optimal injection volume of epineph-rine with high efficacy for hemostasis and low complication rate in patients with actively bleeding ulcers. METHODS: This prospective, randomized, comparative trial was conducted in a medical center. A total of 228 patients with actively bleeding ulcers (spurting or oozing) were randomly assigned to three groups with 20, 30 and 40 mL endoscopic injections of an 1: 10000 solution of epinephrine. The hemostatic effects and clinical outcomes were compared between the three groups. significant differences in all background variables between the three groups. Initial hemostasis was achieved in 97.4%, 98.7% and 100% of patients respectively in the 20, 30 and 40 mL epinephrine groups. There were no significant differences in the rate of initial hemostasis between the three groups. The rate of peptic ulcer perforation was significantly higher in the 40 mL epinephrine group than in the 20 and 30 mL epinephrine groups ( P <0.05). There were no significant (P <0.01). There were no significant changes in recurrent bleeding in the 20 mL epinephrine group (20.3%) than in the 30 (5.3%) and 40 mL differences in the rates of surgical intervention, the amount of transfusion requirements, the days of hospitalization, the deaths from bleeding and 30 d mortality between the three groups. The number of patients who developed epigastric pain due to endoscopic injection, was significantly higher in the Significant elevation of systolic blood pressure after endoscopic injection was observed in the 40 mL epinephrine (P <0.001) 40 mL epinephrine group (51/76) than in 20 (2/76) and 30 mL Significant decreasing and normalization of pulse rates after endoscopic injections were observed in the 20 mL and 30 mL epinephrine groups (P <0.01). CONCLUSION: Injection of 30 mL diluted epinephrine (1: 10000) recurrent bleeding with a low rate of complications. The optimal injection volume of epinephrine for endoscopic treatment of an actively bleeding ulcer (spurting or oozing) is 30 mL.