Background: A triggering infectious agent has long been postulated in rheumatoid arthritis. Data on the possible role of Helicobacter pylori infection are lacking. Aims: To assess the effect of H. pylori eradication in patients with rheumatoid arthritis. Methods: Fifty-eight adult patients with established rheumatoid arthritis and dyspeptic symptoms were recruited - 28 were H. pylori -positive and 30 were H. pylori-negative on the basis of invasive tests. All infected patients were treated successfully. We evaluated the disease activity using clinical and laboratory parameters at baseline and every 4 months during 2 years, and compared the variations in the two subgroups. Results: H. pylori -eradicated rheumatoid arthritis patients showed progressive improvement over time (P < 0.0001) of all clinical indices compared with baseline, whereas H. pylori-negative rheumatoid arthritis patients remained substantially unchanged. After 2 years, H. pylori -eradicated rheumatoid arthritis patients differed significantly (P < 0.04-0.0001) from patients without H. pylori infection in terms of improvement of all clinical parameters. At the same time point, several laboratory indices (erythrocyte sedimentation rate, fibrinogen, alpha(2) -globulins and antinuclear antibody) showed significantly lower values (P < 0.02-0.0003) in the H. pylori-eradicated subgroup compared to the H. pylori -negative subgroup. Conclusions: Our data suggest that H. pylori infection is implicated in the pathogenesis of rheumatoid arthritis, in that its eradication may induce a significant improvement of disease activity over 24 months. H. pylori eradication seems to be advantageous in infected rheumatoid arthritis patients, but controlled studies are needed.