OBJECTIVES: Adding omega-3 acid ethyl esters 90 (O-3EE) to standard therapies in secondary prevention after post myocardial infarction (MI) significantly reduces sudden death. This study evaluates the cost-effectiveness of adding 1g O-3EE to current secondary prevention treatment after acute MI in the Irish and Estonian public healthcare systems. METHODS: Based on GISSI-Prevenzione trial outcomes (MI, stroke, revascularisation rate, mortality), two models for Ireland and Estonia were developed, using a lifetime and 3.5-years (GISSI-Prevenzione trial duration) time horizons with 1-year cycles. Local event costs were based on AR-DRGs (Ireland) and NordDRGs tariffs (Estonia). Life expectancy data (12.9 years) for survivors of cardiac disease (15,590 cases) were obtained from the Saskatchewan database and country-adjusted. Annual discounting of 4% (Ireland) and 5% (Estonia) was applied on outcomes and costs. Incremental cost (€) per life year gained (LYG) and Quality of Adjusted Life years Gained (QALYG) were calculated from the public payer perspective. RESULTS: Lifelong treatment with O-3EE yielded 0.26 LYG, 0.19 QALYG (Ireland) and 0.24 LYG (Estonia) with an additional total direct cost of €1,624 (Ireland) and €1,218 (Estonia) resulting in an incremental cost-effectiveness ratio (ICER) of €6,223/LYG and €8,210/QALYG (Ireland) and €5,079/LYG (Estonia). Respective ICERs at 3.5-years were €18,686/LYG, €23,527/QALYG for Ireland and €28,797/LYG for Estonia. Sensitivity analyses showed that time horizon, discounting and follow-up cost of stroke are sensitive factors. Difference in co-payment for workers and retired patients (Estonia) marginally impacted ICERs. Probabilistic sensitivity analysis showed that the probability for O-3EE to be cost-effective is higher than 95% in Estonia (threshold €32,000/LYG). One-way sensitivity analyses showed strong robustness in Ireland (threshold €20,000/QALY). CONCLUSIONS: The incremental cost-effectiveness ratios indicated that adding 1g O-3EE to standard treatment in secondary prevention post-MI was in the range likely to be considered cost-effective in Ireland and Estonia.