We conducted a prospective randomized trial to evaluate the effectiveness and safety of endoscopic microwave coagulation in comparison to endoscopic sclerosis in the treatment of peptic ulcer bleeding. Over 15 months 127 ulcer-bleeding patients with an actively bleeding vessel (N = 21), a non-bleeding vessel (N = 53), oozing hemorrhage (N = 25), or an adherent clot (N = 28) in the ulcer base were randomly assigned during endoscopy to receive treatment with endoscopic sclerosis or with microwave coagulation. There were no significant differences in effectiveness between endoscopic sclerosis and microwave coagulation in any of the assessed parameters: the percentage of patients with major recurrent hemorrhage (5 vs. 12), the percentage who needed emergency surgery (5 vs. 9), the mean (+/- SD) transfusion requirements (0.32 +/- 0.89 vs. 0.78 +/- 1.65), the mean number of hospital days (10.3 +/- 3.5 vs. 10.7 +/- 4.1), and the number of deaths due to bleeding (0 vs. 2) were similar in both groups. No case of perforation occurred in either group. The data suggest that microwave coagulation is as effective and safe as endoscopic sclerosis in the treatment of bleeding peptic ulcers.