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Introduction: National guidelines for prevention of cardiovascular disease make different recommendations in relation to screening and treating patients with aspirin, antihypertensive treatment and statins. The resource cost and health implications of these differences are quantified in this paper., Data Sources: Guidelines were obtained from Australia, New Zealand, Canada, UK and USA. Effectiveness data were obtained from published sources, costs and a model population of 2000 patients from US sources., Method: The resource costs and health effects of screening and treating a standard population of 2000 persons were determined for each of the five national guidelines. Costs and effects were calculated over a 5-year time horizon and cost-effectiveness determined cost per cardiovascular event prevented., Results: Cost per cardiovascular event prevented is lowest in older patients and very high under 35. The New Zealand guidelines are more cost-effective of the national guidelines, however, they would be more effective if they incorporated US recommendations on the use of aspirin. Further antihypertensive treatment is the least cost-effective of the interventions considered., Discussion: Cardiovascular disease prevention guidelines should focus on older rather than younger patients. Treatment eligibility should be informed more by risk than by individual risk factor status. Guidelines should put greater emphasis on the use of aspirin and initial antihypertensive treatment than on achieving blood pressure targets., Conclusion: In order to justify their recommendations guidelines should quantify the resource implications in relation to the health benefits.