The data regarding the role of Helicobacter pylori infection in patients with bile reflux are conflicting. Bile reflux is often observed after cholecystectomy. This study focuses on the role of H. pylori in gastric pathology of patients who had undergone cholecystectomy. Eighty-seven consecutive patients were included in the study. An upper gastrointestinal endoscopy was performed, and biopsy specimens were taken in the antrum, incisura angularis, and in the gastric body. The presence of bile reflux in gastric fluid at endoscopic examination was recorded. The overall H. pylori infection rate was 62%, with no difference between patients with (59.7%) and without (64%) endoscopic bile reflux (p = 0.67). The intestinal metaplasia rate in gastric mucosa was significantly higher in patients with both H. pylori and bile reflux than in patients without infection and bile reflux (36.4% vs. 5.6%, p = 0.02). Moreover, the mean number of years after cholecystectomy in patients with intestinal metaplasia was significantly higher than in those without metaplasia (21.1 +/- 7 vs. 11.5 +/- 8 years, p < 0.0001), whereas mean age did not differ significantly between groups (60.3 +/- 12 vs. 55.8 +/- 11 years, p = 0.14). Furthermore, we found four cases of gastric cancer, three with H. pylori infection. The mean number of years after cholecystectomy was significantly higher in patients with gastric cancer than in other patients (21.8 +/- 4 vs. 12.2 +/- 8 years, p = 0.009). This study found that H. pylori infection is frequent in cholecystectomized patients, also in the presence of endoscopic bile reflux. Bile reflux seems to act synergistically with H. pylori infection on gastric pathology.