Aims/hypothesis: We estimated cardiovascular disease (CVD) mortality in individuals with the metabolic syndrome on the basis of different definitions. Methods: We collaboratively analysed data from 4,715 men and 5,554 women, who were aged 30 to 89 years, had a maximum follow-up of 7 to 16 years, and were drawn from nine European population-based cohorts. Cox regression analysis with age as time scale was performed to estimate hazard ratio (HR) for mortality, adjusting for cohort, serum total cholesterol and smoking. Results: The prevalence of the metabolic syndrome according to definitions of WHO, the National Cholesterol Education Program (NCEP), NCEP revised and the International Diabetes Federation (IDF) was 27.0%, 25.9%, 32.2% and 35.9% respectively in men and 19.7%, 23.4%, 28.5% and 34.1% respectively in women. The corresponding HRs (95% CIs) for CVD mortality were 2.09 (1.59-2.76), 1.74 (1.31-2.30), 1.72 (1.31-2.26) and 1.51 (1.15-1.99) in men, and 1.60 (1.01-2.51), 1.39 (0.89-2.18), 1.09 (0.70-1.69) and 1.53 (0.99-2.36) in women. The paired homogeneity test showed that in men the HR was higher with the WHO definition than with the IDF definition (p=0.03). In women the HR was lower with the revised NCEP definitions than with either the WHO (p=0.02) or the IDF (p=0.01) definitions. With a few exceptions, HRs for full definitions of the syndrome were not significantly different from those for their single components. Conclusions/interpretation: Metabolic syndrome by the four definitions predicted CVD mortality in men, but the prediction was weak in women. Further research is required on the utility of definitions of the metabolic syndrome above and beyond that of its single components and in individual CVD risk stratification, particularly with regard to sex difference in the prediction.