In an open study the clinical efficacy of famotidine 40 mg on a duodenal ulcer was compared to that of proglumide 1600 mg. The study included 106 patients with acute duodenal ulcer, divided into two groups: A-famotidine and B-proglumide. There were no significant differences between the groups in baseline characteristics. Due to different reasons nine patients were excluded from analysis. Duodenal ulcer diagnosis and healing were determined exclusively by endoscopy. Ulcer healing was observed after four weeks in 40/49 (81.6%) patients in group A and 35/48 (72.9%) patients in group B and in 46/49 (94%) and 40/48 (83.3) after eight weeks, respectively. There were no statistically significant differences between the healing rates for both groups (p > 0.05). The reduction of ulcer related symptoms and antacid consumption was equal in both groups. No adverse effects were reported in the group A, but there were three patients with transient skin rush in the group B. Reported adverse effects were minor and did not merit exclusion from the study. It was concluded that the efficacy of famotidine 40 mg vs. proglumide 1600 mg was similar, although famotidine had proportionally better effect than proglumide. These findings supported the hypothesis that famotidine suppressed acid secretion stronger than proglumide.