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Helicobacter pylori is a gastrointestinal pathogen known to be associated with cardiovascular disease (CVD). However, most analyses about the effect of H. pylori infection have been done in patients with a history of CVD but not in healthy subjects. We evaluated the association between H. pylori infection and subclinical atherosclerosis by using cardiac multidetector computed tomography (MDCT) in healthy subjects without previous CVD. From December 2007 to February 2014, 463 subjects who underwent the rapid urease test (CLO test), pulse-wave velocity (PWV) measurement, and MDCT for a self-referred health check-up were enrolled to this study. Helicobacter pylori infection was defined on the basis of CLO test positivity on endoscopic gastric biopsy. Significant coronary artery stenosis was defined as ≥50% stenosis in any of the major epicardial coronary vessel on MDCT. The CLO-positive subjects had a lower high-density lipoprotein-cholesterol (HDL-cholesterol) level compared to the CLO-negative subjects. The incidence of significant coronary stenosis was higher in the CLO-positive group (7.6% vs. 2.9%, P = 0.01). Furthermore, the number of subjects with coronary artery calcium score >0 and log{(number of segments with plaque)+1} were also significantly higher in the CLO-positive group. However, there was no statistical difference in the number of subjects with coronary artery calcium score >100, the prevalence of any plaque nor the plaque characteristics (calcified, mixed, or soft). Pulse-wave velocity (PWV) was neither associated with CLO test positivity. The CLO-positive group was 3-fold more likely to have significant coronary artery stenosis even after adjusting for confounding factors (adjusted odds ratio 2.813, 95% confidence interval 1.051–7.528, P = 0.04). In a healthy population, current H. pylori infection was associated with subclinical but significant coronary artery stenosis. The causal relationship between H. pylori infection and subclinical atherosclerosis in a “healthy” population remains to be investigated in the future. [ABSTRACT FROM AUTHOR]