Background & Aims: Endoscopic injection therapy improves outcome in bleeding peptic ulcer, but the optimum regimen is unknown, The aim of this study was to compare the efficacy of endoscopic therapy with dilute adrenaline alone vs, adrenaline plus human thrombin in the treatment of patients with major peptic ulcer hemorrhage. Methods: One hundred forty patients with significant peptic ulcer hemorrhage and active arterial bleeding or a nonbleeding visible vessel were randomized to endoscopic injection with 1:100,000 adrenaline (70 patients; group 1) or to adrenaline plus 600-1000 IU of human thrombin (70 patients; group 2), The two groups were well matched for age, shock, hemoglobin concentration, comorbid disease, endoscopic findings, and consumption of nonsteroidal antiinflammatory drugs, Results: Fourteen patients from group 1 (20%) and 3 patients from group 2 (4.5%) rebled (P < 0.005), Seven patients from group 1 (10%) but no patients from group 2 died within 30 days of admission (P < 0.013), Patients from group 1 were administered a total of 297 units of blood compared with 219 units in group 2 (P < 0.041). Conclusions: Endoscopic injection using adrenaline plus human thrombin is superior to injection with dilute adrenaline alone and may represent the best treatment for bleeding peptic ulcers.