BACKGROUND: Immunopathological and inflammatory processes play important roles in the initiation and development of ischemic heart disease. Hence, this study aimed to evaluate the relationship between serum levels rheumatoid factor (RF) and anti-nuclear antibodies (ANA) and severity of coronary stenotic lesions. METHODS: Totally 140 patients with acute coronary syndrome (ACS) (n = 70) and chronic stable angina (CSA) (n = 70) that undergoing coronary angiography were enrolled in this study. ANA by the enzyme-linked immunosorbent assay (ELISA) and serum level of RF was measured by latex method. The severity of coronary stenotic lesions calculated by Gensini score. To analyze the correlations of ANA and RF to Gensini score Pearson correlation test was used. To adjust the effect of age and other confounder factors such hypertension, diabetes, hyperlipidemia and smoking multiple linear regression was used. RESULTS: The mean serum levels of RF and ANA in CSA group were significantly higher than ACS group after adjusting for the confounder factors (P < 0.050 for ANA). Serum levels of ANA significantly correlated with severity of coronary stenotic lesions calculated by Gensini score (r = 0.40 and P < 0.050). After adjusting confounders, multiple linear regression analysis showed ANA remained independently associated with Gensini scores in ACS group (B = 0.505, P < 0.001). CONCLUSION: Higher serum levels of ANA may be considered as independent risk factors for ACS.