Background: The relationship between Helicobacter pylori ( H. pylori) eradication and atrophic changes in the gastric mucosa has not yet been fully defined. Although studies report a partial restoration of serum pepsinogen I (sPGI) levels after eradication, it is not clear if this finding reflects gastric mucosal healing on a morphological level. Aim: To assess alterations in gastric function after H. pylori eradication on moderate/severe body atrophic gastritis by determination of sPGI levels. Methods: Twenty-three dyspeptic patients, selected from 284 consecutive H. pylori positive patients, with histological features of moderate/severe body atrophic gastritis and sPGI < 25 µg/L (11 men, mean age: 51.8 years, range: 29–79 years), underwent an upper gastrointestinal endoscopy with gastric biopsies and sPGI determination at baseline. All patients underwent eradication therapy. Serum pepsinogen I was measured again after 6 months, and at 1, 2, 3 and 4 years after eradication therapy. Results: Mean sPGI levels prior to eradication were 11.9 µg/L (range: 4–23 µg/L). Six months after eradication therapy, mean sPGI levels significantly increased to 17.4 µg/L ( P = 0.04). At the completion of the study, 4 years after eradication, sPGI levels increased from 17.4 to 32.7 µg/L ( P = 0.01). A significant progressive increase in sPGI levels was observed from 6 months to 1 year (17.4 to 23.9 µg/L) and from 1 to 2 years (23.9 to 26.0 µg/L, P = 0.01). Serum pepsinogen I levels higher than the cut-off value of 25 µg/L were observed at various time-points: 6.3% of patients at 6 months (1/16), 33.3% (5/15) at 1 year, 50% (7/14) at 24 months, 66.7% (6/9) at 36 months and 87.5% (7/8) at 4 years. Conclusion: After H. pylori eradication, subjects with body atrophic gastritis showed long-term improvement of physiological gastric function, reflected by significantly and continually increasing sPGI levels over a 4-year period. [ABSTRACT FROM AUTHOR]