To synthesize the available data on the association between metabolic syndrome and all-cause mortality, we conducted a meta-analysis of prospective cohort studies. We performed a literature search using Medline, EMBASE and Cochrane Library from 2001 to December 2009, with no restrictions. We included studies if they were prospective, had an assessment of metabolic syndrome at baseline and risk of all-cause mortality. We recorded several characteristics for each study. We extracted relative risks (RR) and 95% confidence intervals (CI) and pooled them using fixed or random effects models. We performed sensitivity analysis, and assessed heterogeneity and publication bias. A total of 21 studies including 372,411 participants were included in our meta-analysis. 18,556 deaths from any cause occurred during a mean follow-up of 11.5 years. Individuals with the metabolic syndrome, compared to those without, had an increased mortality from all causes (pooled RR 1.46; 95% CI 1.35-1.57). The RR of all-cause mortality associated with metabolic syndrome was higher in studies using the National Cholesterol Education Program Adult Treatment Panel (NCEP) than the revised NCEP criteria (RR: 1.45 vs. 1.25; P = 0.0002). Metabolic syndrome is an important risk factor for all-cause mortality. The diagnosis and treatment of the underlying risk factors for the metabolic syndrome should be an important strategy for the reduction of all-cause mortality associated with metabolic syndrome in the general population.