Pentraxin 3 (PTX3) is a novel candidate immunoinflammatory marker that has been reported to be associated with cardiometabolic risk factors and to predict adverse outcomes in individuals with cardiovascular disease (CVD). Despite being a member of the same pentraxin protein family as C-reactive protein (CRP), PTX3 probably reflects different aspects of CVD pathogenesis. In this study, we assessed plasma PTX3 correlates and determinants in the Health 2000 Survey population, which comprised n = 403 insulin-resistant subjects, n = 845 hypercholesterolaemic subjects and n = 311 hypertensive subjects, all aged between 46 and 76 years. In insulin-resistant subjects the PTX3 concentration was found to correlate directly with age, pulse pressure and indoleamine 2,3-dioxygenase (IDO) enzyme activity and inversely with total and low-density lipoprotein (LDL) cholesterol. In hypercholesterolaemic subjects, the PTX3 concentration correlated directly with HDL cholesterol, systolic blood pressure and pulse pressure, whereas in hypertensive subjects, the PTX3 concentration correlated directly with systolic blood pressure, pulse pressure and IDO activity. No correlation was observed between the concentrations of PTX3 and CRP, adiposity indicators or indicators of subclinical atherosclerosis in any of the subject groups. PTX3 concentration variations were attributed to variations in LDL cholesterol and IDO activity in insulin-resistant subjects and to pulse pressure in hypercholesterolaemic and hypertensive subjects. These results indicate that, in individuals at high risk of CVD, the PTX3 concentration is associated with cardiovascular risk factors but not with subclinical atherosclerosis.