OBJECTIVES: Low-dose Aspirin is standard care in patients with cardiovascular disease (CVD). In primary prevention the use of Aspirin is not fully established although meta-analyses and guidelines support its use in persons at increased CVD risk. This study assessed the health economic consequences of the use of low-dose Aspirin in the primary prevention of CVD in the UK, Germany, Spain and Italy. METHODS: Based on results reported in two meta-analyses, a Markov model was developed to predict the cost-effectiveness of Aspirin in the primary prevention of CVD. Different time horizons (1 to 10 years), 1-year cycles and direct costs from the health care payer's perspective (2003) were used. Effects were expressed in Life-Years (LY) and QALY. Utility data (TTO) were obtained from published data. Country specific discounting was applied. RESULTS: For patients with an annual risk of coronary heart disease (CHD) of 1.5%, the model results in average savings with low-dose aspirin after 10 years of €201 [95%CI €81–€331], €281 [95%CI €141–€422], €797 [95%CI €301–€1331] and €427 [95%CI €122–731] per patient in the UK, Germany, Spain and Italy, respectively. Although the savings in the first year are modest (on average €10-€20), from the second year on they are significant in all countries. Sensitivity analysis showed the results robustness. The number of LY and QALY gained with aspirin were respectively 0.2 and 0.4 years in the four countries. Monte Carlo analysis showed aspirin-dominance in ±97% of cases for the three studied annual risks of CHD (0.6%, 1.0% and 1.5%) except for Italy, where dominance in ≥95% was seen at annual risks of 1% and 1.5%. CONCLUSIONS: Administering low-dose Aspirin to patients with an annual risk of CHD of ≥1% is significantly cost-saving from the health care payer's perspective in all countries analysed. Savings start after one year of treatment.