INTRODUCTION Fetuin-A has been described to correlate inversely with vascular calcification both in animal models but also in patients with heart and renal disease. In this current study, we sought to investigate whether fetuin-A might be a useful marker for the discrimination of ischemic (ICM) from dilated cardiomyopathy (DCM). METHODS A total of 124 non-consecutive patients were included in this study, 59 patients suffered from ICM and 65 patients from DCM. Serum samples were obtained during out-patient visits and analyzed for fetuin-A by ELISA. RESULTS Median fetuin-A concentration in the overall cohort was significantly lower in ICM patients compared to DCM patients (62.2±16.4 μg/mL vs. 129.6±56.6 μg/mL; P<.001). A positive correlation of fetuin-A levels was found with BMI, cholesterol, LDL/HDL ratio and triglycerides and an inverse correlation with age (r=-.36; P<.001). Moreover, patients suffering from (stable) angina pectoris evidenced lower fetuin-A levels compared to non-symptomatic patients (73.1±22.7 μg/mL vs. 83.7±26.2 μg/mL; P=.047) CONCLUSIONS: Fetuin-A was shown to be a potential discriminator and biomarker for the differential diagnosis between ICM and DCM. Fetuin-A levels might also be helpful in the process of diagnostic decision-making in regards to invasive management or medical therapy.