Atrial fibrillation (AF) is the most common rhythm disturbance seen in clinical practice. Evidence emerged that suggested inflammation was associated with risk of AF. Helicobacter pylori causes gastric and esophageal inflammation, as well as systemic and vascular inflammation. These local and systemic inflammatory effects may increase the risk of AF. Study patients were consecutive patients who underwent angiography for suspicion of coronary artery disease. Patients' AF status was determined by a search of hospital discharge summaries for diagnostic International Classification of Diseases, Ninth Revision codes for AF, assessment of previous electrocardiograms at the index and previous admissions to LDS Hospital (Salt Lake City, Utah), and search of the electrocardiographic database of LDS Hospital. In addition to routine laboratory studies, serum was analyzed to determine H pylori serostatus and index C-reactive protein (CRP) level. A total of 943 patients with known AF status were studied. Those with AF tended to be older (70.9 +/- 9.5 vs 63.9 +/- 10.7 years; p <0.001) and had a higher prevalence of congestive heart failure (28% vs 11%; p <0.001). In addition, patients with AF were more likely to be seropositive for H pylori in comparison to the seronegative group (65% vs 55%; p = 0.049). Mean CRP was similar between those with and without AF (2.2 +/- 2.7 vs 2.3 +/- 2.4 mg/dl; p = 0.79). There was no apparent association between H pylori serostatus and CRP. Multivariate predictors of AF included age (hazard ratio [HR] 1.07 per year, 95% confidence interval [CI] 1.04 to 1.10, p <0.0001) and heart failure (HR 2.87, 95% CI 1.59 to 5.18, p <0.0001). H pylori added to the model was marginally associated with AF (HR 1.53, 95% CI 0.95 to 2.47, p = 0.08) when not accounting for age. However, younger patients (<50 years) who were H pylori seropositive had a higher relative risk of AF (8%) versus those who were seronegative (0%). In comparison, older patients seropositive for H pylori had only a modest increased risk of AF (17.5% vs 15.4%; p = 0.11). In conclusion, these data showed a general association of H pylori and AF in patients with multiple cardiovascular risk factors. The association did not persist after accounting for other risk factors. Although older age was highly associated with AF risk in this population, H pylori was additive across 3 distinct age groups, with the highest risk conveyed in the younger cohort.