Moderate wine consumption has been shown to reduce cardiovascular (CV) risk, due to alcohol and polyphenolic compounds, such as resveratrol. We investigated the associations between total urinary resveratrol metabolites (TRMs) as biomarkers of wine and resveratrol consumption and CV risk factors in a large cross-sectional study including high CV risk individuals in Spain. We studied 1000 participants in the PREDIMED Study in whom TRMs were analyzed by LC-MS/MS with a previous solid phase extraction. Multiple linear regression of TRMs (biomarker of wine consumption) improved the mean (95% CI) of HDL [0.168 (0.027-0.309); P=0.02] and triglyceride [-1.012 (-1.797 to -0.227); P=0.012] plasma concentrations and heart rate [-0.259 (-0.412 to -0.107); P<0.001]. Models of TRMs adjusted for alcohol (biomarker of resveratrol intake) decreased fasting blood glucose [-0.533 (-1.034 to -0.033); P=0.037] and triglyceride [-1.014 (-1.998 to -0.029); P=0.044] concentrations, and heart rate [-0.277 (-0.467 to -0.087); P=0.004]. Both resveratrol and wine intake, evaluated as TRMs, were associated with beneficial changes in blood lipid profiles, fasting blood glucose (only resveratrol) and heart rate, suggesting that resveratrol intake via wine consumption might help to decrease CV risk factors.