Epidemiological studies have shown a positive correlation between coronary artery disease (CAD) and gastric Helicobacter pylori (H. pylori) infection. The possible mechanism by which H. pylori could increase the risk of CAD is chronic inflammation. More virulent H. pylori strains bearing the cytotoxin associated gene-A (CagA) can induce much more inflammation than CagA negative strains. The aim of our study was to assess the role of virulent H. pylori strains and inflammatory response in the pathogenesis of CAD. We studied 30 patients with CAD, age and sex being matched with 30 controls of similar social class. We determined the presence of H. pylori infection by rapid urease test, histology and serology (anti-H. pylori IgG). CagA status, serum tumor necrosis factor-alpha (TNF-α), gastrin and fibrinogen levels were also studied. The presence of H. pylori infection was statistically equal in CAD group (93.3%) and controls (86.6%)(p = 0.705). Serum CagA titers were 28.13 ± 9.21 U and 18.32 ± 5.8 U in the CAD and control group respectively. Serum TNF-α levels were 15.21 ± 4.30 pg/ml in the CAD group and 5.36 ± 2.41 pg/ml in the control group. Serum CagA and TNF-α levels showed a significant difference between the two groups (p = 0.000). Patients with CAD had a higher prevalence of CagA-positive strains than controls (67.8% versus 42.3%; p = 0.021). The serum gastrin level was higher in CAD but there was no significant difference between two groups (p = 0.379). Fibrinogen levels of the CAD group were significantly higher than those of the control (370 ± 51 mg/ml and 247 ± 43 mg/ml, p = 0.001). Further more, numbers of occluded vessels in CAD patients were positively correlated with both cagA positivity and TNF-α levels. In conclusion, CagA bearing strains of H. pylori may increase the risk of CAD by inducing chronic inflammation and increasing the expression of cytokines and procoagulant substance.