Despite significant progress in the prevention and treatment of cardiovascular disease, sudden cardiac death (SCD) is a major public health problem. Statins showed consistent benefits on cardiovascular events, but scant data were available about their effects on SCD. This meta-analysis aimed to assess the effect of statins on SCD. Additional analyses were carried out to evaluate lipid reduction as a possible mediator of the effect. Randomized controlled trials from January 1966 to July 2006 were retrieved by searching the MEDLINE database. Inclusion criteria were outcome focusing on the incidence of SCD, statin treatment compared with placebo or no treatment, randomized design, >or=100 patients enrolled, and follow-up>or=6 months. Data were independently abstracted by 2 investigators using a standardized protocol. Ten randomized controlled trials enrolling a total of 22,275 patients were included in the meta-analysis. Risks of SCD were 3% in patients receiving statins and 3.8% in control patients. Statin treatment was associated with a significant 19% risk reduction for SCD (odds ratio 0.81, 95% confidence interval 0.71 to 0.93, p=0.003). In subgroup analysis, the benefit of statins was independent from the main characteristics of the studies and changes in patient lipid levels during the study. In conclusion, our results suggest that statins decrease the risk of SCD.