Background: Although eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been known to have beneficial effects on cardiovascular diseases, the relationship between their levels and mortality after acute myocardial infarction (MI) has not been evaluated prospectively. Methods: We measured the contents of plasma phospholipid EPA and DHA (% of total fatty acids) in 548 patients (391 males; 157 females; mean age, 63yrs) with MI whose blood samples obtained at acute phase of MI. Clinical and biomarker predictors for mortality were identified by Cox regression model. Results: During the mean follow-up of 16 months, 45 (8.2%) patients died. Unadjusted mortality rate was significantly higher in patients with lower tertile of % EPA content (Log rank p=0.003, Fig), but not with lower tertile of % DHA content (Log rank p=0.38). After controlling of confounding variables, age (HR: 1.08, p< 0.001), renal insufficiency (HR: 2.98, p=0.007) and EPA content (HR: 0.33, p=0.009) were found to be independent predictors of mortality. When subdivided by gender, age (HR: 1.08, p=0.001) and renal insufficiency (HR: 4.31, p=0.004) were independent prognostic factors in males whereas in females, only EPA content (HR: 0.12, p=0.002) were identified as a significant predictor for mortality. Conclusions: Lower plasma phospholipid EPA content was an independent predictor for mortality in patients with acute MI. The prognostic value of EPA was more prominent in female patients.