Introduction: A promising concept in cardiovascular disease prevention (the polypill) was introduced in 2003. Although the polypill may seem as an effective intervention, data on its costs and cost effectiveness remain unknown. The aim of this study was to determine the maximum price of the polypill for it to be a cost effective alternative in the primary prevention of cardiovascular disease. Methods: Data on the hypothetical effects of the polypill were taken from the literature. Using data from the Framingham heart study and the Framingham offspring study, life tables were built to model the assumed benefits of the polypill. Using a third party payer perspective and a 10 years time horizon, the authors calculated what should be the maximum drug cost of the polypill for it to be cost effective (using a €20 000/year of life saved threshold) in the primary prevention of cardiovascular disease among populations at different levels of absolute risk of coronary heart disease and age. Results: To be cost effective among populations at levels of 10 year coronary heart disease risk over 20% (high risk), the annual cost of medication for the polypill therapy should be no more than €302 or €410 for men at age 50 and 60 years respectively. For cost effective prevention in populations at levels of coronary heart disease risk between 10% and 20% the costs should be two to three times lower. Conclusion: Although the polypill could theoretically be a highly effective intervention, the costs of the medication could be its caveat for implementation in the primary prevention of cardiovascular disease.