The aim of the present work was to evaluate the association between fish consumption and the development of left ventricular systolic dysfunction in patients who have had an acute coronary syndrome (ACS). During 2006 to 2009, 934 consecutive ACS patients were included in the study; 437 patients who developed LVSD, 347 male (64 +/- 13 y) and 90 female (71 +/- 12 y), and 497 patients with preserved systolic function, 388 male (62 +/- 12 y) and 109 female (66 +/- 12 y). Detailed information regarding their medical records, anthropometric data, physical activity, and smoking habits were recorded. Nutritional habits were assessed using a semiquantitative food-frequency questionnaire. Multi-adjusted analysis revealed that moderate fish consumption was associated with 53% (95% CI: 0.22 to 0.97) lower likelihood of developing left ventricular systolic dysfunction, compared to no/rare consumption, after adjustment for various confounding factors. Furthermore, moderate fish consumption was associated with lower values of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (P = 0.05) and oxidized LDL cholesterol (P = 0.02) in patients who did not develop left ventricular systolic dysfunction. Moderate fish consumption seems to offer significant protection against the development of systolic dysfunction in post ACS patients, merely attributed to its beneficial effect on oxidation process and endothelial function.