BACKGROUND Vitronectin (VN), malondialdehyde (MDA) and high-sensitivity C-reactive rotein (hs-CRP) are cooperative agents involved in the atherosclerosis process. The study was conducted to assess the correlation of VN, MDA and hs-CRP with the severity of coronary artery disease (CAD). METHODS Parameters such as serum VN, MDA and hs-CRP were measured in 250 subjects including 200 patients with angiographically diagnosed CAD (50 subjects with non-significant CAD, 50 with single vessel disease, 50 with double vessel disease, and 50 with triple vessel disease) and 50 CAD-free subjects as a control group. Serum VN was measured with ELISA; MDA was measured based on reaction with thiobarbituric acid (TBA); and hs-CRP level was measured by a Commercial Kit by Immunoturbidimetry. RESULTS Serum VN, MDA and hs-CRP were significantly higher in patient groups compared to control group (P < .05). The mean value of MDA between 1 vessel and 3 vessel groups had significant difference (P = .01), also mean value of MDA between 2 vessel and control group and normal group showed significant difference (P < .001). The difference of MDA between 3 vessel and normal and 1 vessel and control group was significant (P < .001). CONCLUSIONS The association and correlation between VN, MDA and hs-CRP indicate their involvement in the atherosclerosis process that may lead to progression of CAD. Also, these findings suggested that serum levels of VN, MDA and hs-CRP can help as diagnostic and monitoring markers in CAD patients and as markers of disease severity.