Objective: The hazardous effects of heavy metal on cardiovascular diseases were shown in previous studies. The aim of the present study is to test the diagnostic role of plasma and hair heavy metals in severe coronary artery disease (CAD). Materials and Methods: 64 patients undergoing coronary angiography were included in this study. According to the coronary angiography results, patients with severe coronary stenosis (>= 70%) were included in the significant CAD group (n = 34). Patients with non-significant stenosis (< 70%) or normal coronary arteries were included the control group (n = 30). Plasma and hair copper (Cu), zinc (Zn), manganese (Mn), and chromium (Cr) levels were measured in all patients. Results: There was a significant correlation between hair and plasma levels of Cr (r = 0.71, p < 0.001), Zn (r = 0.33, p = 0.007), and Mn (r = 0.28, p = 0.024). Hair analysis showed no significant difference between two groups for the levels of Cr, Mn, Cu, and Zn. However, plasma Cr, Mn, Cu, and Zn levels were significantly higher in the significant CAD group compared to the control group (p < 0.001 for each heavy metal). ROC curve analysis showed sensitivity values of 85% for plasma Mn and Zn for diagnosis severe CAD. In multivariate analysis, plasma Mn (Exp (B): 15.233, p < 0.001) and Zn (Exp (B): 1.658, p < 0.013) levels were significantly associated with significant CAD. Conclusions: Although the underlying mechanisms remain obscure, plasma heavy metal levels are associated with severe CAD. Our results suggest that plasma heavy metal levels may serve as a useful marker for diagnosing severe CAD.