Background: We sought to compare metabolic syndrome (MetS) with the Framingham Risk Score (FRS) as predictors of coronary heart disease (CHD), stroke, and type 2 diabetes mellitus (DM2) in middle-aged men. Methods: A prospective study of 5128 men aged 40 to 59 years with no history of cardiovascular disease (CVD) (CHD or stroke) or DM2 drawn from general practices in 24 British towns and observed for 20 years. Metabolic syndrome was defined as the presence of 3 or more metabolic abnormalities based on modified National Cholesterol Education Program criteria. Results: Men with MetS at baseline (26%) showed significantly higher relative risk (RR) than men without MetS of developing CHD (RR, 1.64; 95% confidence interval [CI], 1.41-1.90), stroke (RR, 1.61 95% CI, 1.26-2.06), and DM2 (RR, 3.57; 95% CI, 2.83-4.50). The probability of developing CVD or DM2 over 20 years increased from 11.9% in those with no abnormalities to 31.2% in those with 3 abnormalities to 40.8% in those with 4 or 5 abnormalities. The FRS was a better predictor of CHD and stroke than MetS but was less predictive of DM2. Areas under the receiver-operating characteristic curves for FRS vs the number of metabolic abnormalities were 0.68 vs 0.59 for CHD, 0.60 vs 0.70 for DM2, and 0.66 vs 0.55 for stroke (P<.001 for all). Conclusions: Presence of MetS is a significant predictor of CVD and DM2 but is a stronger predictor of DM2 than of CHD. Although MetS does not predict CHD as well as the FRS, it serves well as a simple clinical tool for identifying high-risk subjects predisposed toCVDor DM2.