Aims: To compare the impact of three major guidelines for the prevention of cardiovascular disease (CVD). Methods and results: 21,263 men and women aged 39-79 years from the EPIC (European Prospective Investigation of Cancer) Norfolk cohort were retrospectively classified at baseline by statin therapy recommendations according to the NICE, ESC and ATPIII CVD prevention guidelines. Recommendations based on baseline data were related to 10-year follow-up to calculate number of new CVD events that could be prevented by statins, number-needed-to-treat (NNT) and CVD incidence decrease. Statin therapy was Conclusions: The NICE guideline selected greater percentages of elderly and subjects with prevalent CVD risk factors. It performed best in recommending statins and could have prevented the greatest number of CVD events. With all guidelines, nearly half the subjects who developed a CVD event were not considered eligible for statins at baseline. Less selective prevention strategies need to be explored.