We estimated the rate of Helicobacter pylori "reappearance" and of duodenal ulcer relapse up to 6 years after eradication of H. pylori. Of 220 patients in whom H. pylori was eradicated, 165 were eligible at 12 months to follow-up. Endoscopy was scheduled every 12 months or whenever symptoms appeared. Baseline H. pylori eradication was confirmed by CLO test, histology (hematoxylin-eosin and Giemsa stain), and culture. H. pylori was tested for by the three methods at 12 months and subsequently by 2 methods (CLO, histology) on biopsies obtained from the gastric antrum and body. We reviewed 90 patients after 1 year, 32 after 2 years, 13 after 3 years, 12 after 4 years, 2 after 5 years, and 16 after 6 years (range, 12 to 72 months; average, 25.23 months; patient-years, 347). At 12 months after eradication, 16 of 165 patients (9.7%) were H. pylori positive and 5 had ulcer relapse. Of 75 patients evaluated at 24 months, 7 (9.3%) were H. pylori positive and 1 (1.3%) had ulcer relapse. At 36 months, 43 patients were seen and 1 (2.3%) was H. pylori positive and had ulcer relapse (2.3%). Thirty, 18, and 16 patients were seen at 48, 60, and 72 months, respectively. None was H. pylori positive and none had ulcer relapse. Overall, 24 H. pylori-positive patients were found, two thirds of them in the first year after eradication. In 7 of 24 (29%, 6 smokers), ulcer recurred. None of the H. pylori-negative patients had ulcer relapse. The H. pylori reappearance rate was 7% and the ulcer relapse rate was 2% per patient-year. If the 16 H. pylori-positive patients who were found the first year are considered as recrudescence, then the reinfection rate will be 2.3% per patient-year.