The objective of the present work was to determine the effect of treating Helicobacter pylori infection on the recurrence of peptic ulcer bleeding. We prospectively followed 66 out of 70 consecutive H. pylori-positive (histology and/or culture) patients with conservatively and endoscopically managed peptic ulcer bleeding (duodenal ulcer; n = 39, gastric ulcer: n = 25, gastroduodenal double ulcer: n = 2) for a median period of 17 months (range 6-33 months). Patients were treated in seven different clinical protocols, each of which included the attempt to eradicate H. pylori infection. Patients with (n = 42) and without (n = 24) bacterial eradication had similar demographic and clinical characteristics. Eradication of H. pylori was associated with a statistically significant reduction of ulcer recurrences (2.4 vs. 62.5%; p < 0.001) and bleeding relapses (0 vs. 37.5%; p = 0.01). We conclude that H. pylori eradication markedly changes the natural history in patients with complicated duodenal and gastric ulcer disease. Thus, treatment aimed at bacterial eradication should be considered in all patients with conservatively managed bleeding from H. pylori-positive ulcers.