Background Mechanisms underlying the association between grip strength and cardiovascular mortality are poorly understood. We aimed to assess the association of grip strength with a panel of cardiovascular risk markers. Design The study was based on a cross-sectional analysis of 3468 adults aged 50-75 years (1891 women) from a population-based sample in Lausanne, Switzerland. Methods Grip strength was measured using a hydraulic hand dynamometer. Cardiovascular risk markers included anthropometry, blood pressure, lipids, glucose, adiposity, inflammatory and other metabolic markers. Results In both genders, grip strength was negatively associated with fat mass (Pearson correlation coefficient: women: -0.170, men: -0.198), systolic blood pressure (women: -0.096, men: -0.074), fasting glucose (women: -0.048, men: -0.071), log-transformed leptin (women: -0.074, men: -0.065), log-transformed high-sensitivity C-reactive protein (women: -0.101, men: -0.079) and log-transformed homocysteine (women: -0.109, men: -0.060). In men, grip strength was also positively associated with diastolic blood pressure (0.068), total (0.106) and low density lipoprotein-cholesterol (0.082), and negatively associated with interleukin-6 (-0.071); in women, grip strength was negatively associated with triglycerides (-0.064) and uric acid (-0.059). After multivariate adjustment, grip strength was negatively associated with waist circumference (change per 5 kg increase in grip strength: -0.82 cm in women and -0.77 cm in men), fat mass (-0.56% in women; -0.27% in men) and high-sensitivity C-reactive protein (-6.8% in women; -3.2% in men) in both genders, and with body mass index (0.22 kg/m javax.xml.bind.JAXBElement@165be361 ) and leptin (-2.7%) in men. Conclusion Grip strength shows only moderate associations with cardiovascular risk markers. The effect of muscle strength as measured by grip strength on cardiovascular disease does not seem to be mediated by cardiovascular risk markers.