Background- Atherosclerosis is a dynamic and progressive disease arising from the combination of endothelial dysfunction and inflammation. So, inflammatory mediators are important causative and progressive factors in atherosclerosis. Interleukin-18 (IL-18) is a pleiotropic cytokine which may have a key role in atherosclerosis, because the results of recent studies indicated that IL-18, either directly as a pro-inflammatory factor or indirectly as an interferon inducing factor, has central role in the inflammatory cascade. In present study, we evaluated the relation between blood concentration of IL-18 with atherosclerosis and its severity and also the relation of this cytokine with the other known risk factors of coronary artery disease (CAD). Methods - 138 patients, who underwent diagnostic cardiac catheterization and had the inclusion criteria for this study, were selected. In the beginning, a questionnaire containing personal information and medical history was completed for each of them and blood samples were collected 24 hours before catheterization. We measured blood level of IL-18 and CRP in all samples. The results of these tests and the angiography were entered in the questionnaire and then information was analyzed using regression analyzing, K2 and statistical T test. P values of<0.05 were considered statistically significant. Results- By using the results of angiography, patients were divided in two groups. 1- Control group or normal coronary arteries (32 people) 2- Case group (106 people) or patients who were suffering from CAD. In second group, 6 patients (5.6%) had minimal CAD, 44 patients (41.5%) had single-vessel disease (SVD), 27 patients (25.4%) had 2VD and 29 patients (27.5%) had 3VD. In the laboratory tests, the mean IL-18 blood level in patients with CAD was 258.1 pgr/ml but in normal coronary arteries group it was 216.6 pgr/ml. The average blood level of IL-18 in patients who had minimal CAD was 235.5 pgr/ml, in SVD was 247.2 pgr/ml, in 2VD was 263.7 pgr/ml and in patients with 3VD was 274.1 pgr/ml. Also average CRP blood level in normal group was 8.9 mgr/L while in patients with CAD it was 20.4 mgr/L. Conclusion- The results of this study indicated that there was a direct and significant correlation between blood IL-18 level with existence (P<0.001) and severity of CAD (P<0.01) and IL-18 can be an independent predictor risk factor of atherosclerosis.