Patients who survive an acute myocardial infarction (MI) are at increased risk of subsequent major cardiovascular events and cardiac (often sudden) death. The use of highly purified omega-3 polyunsaturated fatty acids (n-3 PUFAs) in addition to standard secondary prevention after MI results in a significant reduction in risk of sudden death. OBJECTIVE: To assess the cost-effectiveness of adding n-3 PUFAs to the current secondary prevention treatment after acute MI in five countries (Australia, Belgium, Canada, Germany, Poland). METHODS: Based on the clinical outcomes of GISSI-Prevenzione (MI, stroke, revascularisation rate and mortality), a decision model was built in DataProTM. The implications of adding n-3 PUFAs to standard treatment in patients with a recent history of MI were analysed from the health care payer's perspective. The time horizon was 3.5 years (identical to GISSI-Prevenzione). Event costs were based on literature data. Life expectancy data for survivors of cardiac disease were obtained from the Saskatchewan database and country-adjusted. Results are expressed as extra cost (Euro) per life year gained (LYG). Country-specific discounting was applied to costs and effects. RESULTS: Treatment with n-3 PUFAs yielded between 0.265 (Poland) and 0.289 (Canada) LYG, at an additional cost of 823Euro (Canada) to 1479Euro (Belgium). The incremental cost-effectiveness ratio (ICER) varied between 2850Euro (Canada) and 5154Euro (Belgium) per LYG. Sensitivity analyses on effectiveness, cost of complications and discounting proved the robustness of the results. A second order Monte Carlo simulation based on the 95% CIs obtained from GISSI showed that n-3 PUFAs are cost-effective in more than 99% of patients (threshold 20,000Euro/LYG). Including costs incurred during LYG considerably increased total costs, but had no impact on the ICER-based treatment recommendation. CONCLUSIONS: Adding highly purified n-3 PUFAs to standard treatment in the secondary prevention after MI appears to be cost-effective in the five countries studied.