The role of metabolic syndrome and associated haemostatic and inflammatory markers in risk of atherosclerosis in different vascular beds is controversial. We used modified National Cholesterol Education Program criteria to define metabolic syndrome in a population-based cohort of men and women aged 55-74 years with up to 15 years of follow-up to investigate whether metabolic syndrome is associated with risk of cerebrovascular and peripheral arterial disease and the role of inflammatory and haemostatic factors in these relationships. Data were available for 762 participants, of whom 267 (35%) had metabolic syndrome at baseline and 69 (9.0%) and 108 (14%) had cerebrovascular and peripheral arterial disease events, respectively, during follow-up. We used Cox proportional hazards modelling to estimate hazard ratios (HRs). Metabolic syndrome was associated with several haemostatic and inflammatory variables and with cerebrovascular disease both after adjusting for age and sex (HR 2.12 (1.31-3.41) and after further adjustment for conventional cardiovascular risk factors and inflammatory and haemostatic markers (HR 1.77 (1.05-2.96). The association between metabolic syndrome and peripheral arterial disease was not statistically significant either with adjustment for age and sex (HR 1.33 (0.90-1.96) or after full adjustment (HR 0.89 (0.57-1.38). We conclude that metabolic syndrome was more strongly related to risk of atherosclerosis in the cerebrovascular than the peripheral circulation and the association was independent of conventional risk factors, haemostatic and inflammatory markers in this population. Improving insulin sensitivity may reduce cerebrovascular disease risk.