Cell-free circulating DNA (cf-DNA) has recently arisen as a promising biomarker in acute cardiovascular pathologies and a as mortality predictor in myocardial infarction. We wanted to investigate whether the baseline cf-DNA concentration could serve as an indicator of increased cardiovascular risk and early atherosclerosis. The study population consisted of 1,337 participants (aged 46-77 years) in the Health 2000 Survey. cf-DNA was quantified directly in plasma using the fluorescence-based Quant-iT™ high-sensitivity DNA assay kit. Increased cf-DNA levels paralleled a cluster of cardiometabolic risk factors, such as high blood pressure, unfavorable lipid metabolism profile and systemic inflammation in both sexes. In addition, higher cf-DNA levels indicated decreased arterial elasticity and glucose intolerance in women not using hormonal replacement therapy (HRT). Hence, we conclude that cf-DNA could provide an auxiliary biomarker in cardiometabolic risk assessment and serve as an indicator of arterial stiffness in women not using HRT.