Background: Intermedin (IMD) is involved in the prevention of atherosclerotic plaque progression, possessing cardioprotective effects from hypertrophy, fibrosis and ischemia-reperfusion injury. Elevated plasma IMD levels have been demonstrated in patients with acute coronary syndromes. No human study has examined the role of IMD in stable patients who underwent diagnostic coronary angiography with suspicion of coronary artery disease (CAD). Thus we investigated the role of IMD as a biomarker to discriminate patients with CAD and predict those with severe disease who require early and intensive therapeutic intervention before presenting with acute coronary syndrome., Methods: Eligible two hundred and thirty-eight consecutive patients (123 males, mean age 58.4 ± 10.0 years) who underwent first-time diagnostic coronary angiography were included in this study. Plasma concentrations of IMD were measured from arterial blood samples by the enzyme-linked immunosorbent assay. Patients were divided into three groups according to the presence and degree of CAD, consisting of 48 patients with normal coronary anatomy (Group 1), 111 patients with < 50% coronary stenosis (Group 2), and 79 patients with ≥ 50% stenosis in at least one of the major coronary arteries (group 3). The severity and extent of CAD was evaluated by calculations of the vessel, Gensini, and SYNTAX scores., Results: Circulating plasma IMD levels in patients with CAD were significantly higher than those in patients without CAD (157.7 ± 9.6, 134.8 ± 11.9, and 117.6 ± 7.9 pg/mL in groups 3, 2 and 1 respectively; p < 0.001). Besides, plasma IMD levels were correlated with Gensini and SYNTAX scores (rs = 0.742, and rs = 0.296, respectively; p < 0.05). The presence of ≥50% coronary artery stenosis could be predicted if a cut-off value of 147.7 pg/mL for plasma IMD was used with 88.6% sensitivity and 88.7% specificity. Moreover, a plasma IMD level of <126.6 pg/mL could discriminate a patient with normal coronary arteries from patients with angiographically proven CAD with a sensitivity and specificity of 84.7%, and 83.3% respectively., Conclusions: We demonstrated that IMD might be used as a biomarker to predict CAD and its severity in patients who underwent first time diagnostic coronary angiography.