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Objectives Cytotoxic associated gene-A (CagA)-positive strains of Helicobacter pylori emerged as a possible atherosclerotic stimulus. Nevertheless, whether CagA-positivity is associated with more extensive or severe atherosclerotic coronary burden has never been studied. Methods Forty consecutive patients with coronary artery disease (CAD) and twenty consecutive patients with normal coronary arteries undergoing coronary angiography were enrolled. All patients underwent evaluation of classical atherogenic risk factors and assessment of anti-urease B and anti-CagA antibodies titer. Either the severity of coronary stenosis (stenosis score) or the extent of coronary atherosclerosis (extent score) was evaluated in CAD patients. Results The anti-CagA antibody titer was significantly higher in patients with CAD as compared with normal coronary arteries patients [85 (10-108.75) vs. 47.3 (17-64) RU/ml, P=0.02], whereas there were no differences in anti-urease B titer between the two groups. A significant correlation was found between anti-CagA antibody titer and extent score (R=0.35, P=0.03), whereas stenosis score was similar (R=0.25, P=0.11). On the contrary, no significant correlation was found between anti-urease B antibody titer and either extent or stenosis score. Moreover, CagA-positive patients had a more extensive CAD (P=0.029) when compared with CagA-negative patients. Interestingly, whereas serum glucose, LDL levels, anti-urease B, and anti-CagA antibodies were predictors of extent score at univariate analysis, at multivariate analysis anti-CagA antibody titer only was an independent predictor of the extent of coronary atherosclerosis (B=0.051, standard error of B=0.042, P=0.04). Conclusion These results support the association between CagA-positive H. pylori infection and coronary atherosclerotic burden. Further studies are needed to better elucidate the mechanism by which CagA-positive strains may promote atherosclerosis.