Objective Metabolic syndrome (MetS) is a condition characterized by a cluster of metabolic disorders and is associated with increased risk of cardiovascular disease (CVD). Methods Study subjects were chosen from the Korean Health and Genome Study (KHGS). A total of 8,898 subjects (4,241 males and 4,657 females), 40 to 69 years of age, were enrolled and evaluated for the development of new onset CVD from 2001 to 2012 (median 8.1 years of follow-up). Results The prevalence of MetS at baseline was 22.0% (932/4241) and 29.7% (1383/4657) in males and females, respectively. MetS was associated with increased risk of coronary heart disease (CHD) (HR 1.818, 95% CI 1.312~2.520 in males; HR 1.789, 95% CI 1.332~2.404 in females) and CVD (HR 1.689, 95% CI 1.295~2.204 in males; HR 1.686, 95% CI 1.007~2.192 in females). Specifically, MetS was associated with risk of future stroke in females only (HR 1.486, 95% CI 1.007~2.192, P = 0.046). Among MetS components, abdominal obesity and hypertension were independent predictors of both CHD and CVD. In addition, a higher number of MetS components correlated with higher CVD risk. Conclusion MetS is a significant risk factor for the development of CVD although its impact varies between sexes.