Background: Endoscopic therapy reduces the recurrence of bleeding from actively bleeding peptic ulcers and those with visible vessels. However, the use of endoscopic therapy for ulcers with adherent clots remains controversial. The purpose of this study was to determine whether removal of clot from an ulcer and endoscopic therapy reduces the frequency of recurrent bleeding. Methods: Patients with acute upper GI bleeding from peptic ulcers with adherent clots and no active bleeding were enrolled in a multicenter study. At each center patients were stratified for age, use of nonsteroidal anti-inflammatory drugs, and ulcer location, and were randomized to endoscopic or medical management. Endoscopic therapy consisted of injection of the base of the adherent clot with a solution of epinephrine and mechanical removal of the clot. The base of the ulcer and any stigmata of bleeding were then coagulated until cavitation and adequate coagulation were obtained. Patients in both groups received standard medical therapy for peptic ulcer. Patients were evaluated for recurrence of bleeding for 1 month. Results: Fifty-six patients were enrolled. Rates of recurrent bleeding were 34.3% (12/35) in the medical treatment arm versus 4.8% (1/21) in the endoscopic treatment arm (p < 0.02). Conclusions: In patients with GI bleeding caused by gastric or duodenal ulcers with an adherent clot found on endoscopy, endoscopic therapy with injection of the base of the clot, clot removal, and heat probe coagulation significantly reduces the rate of recurrent bleeding compared with medical therapy alone.