AIMS: Evidence is accumulating for a cardioprotective effect of fish or its n-3 fatty acids, eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA). We examined EPA plus DHA and fish intake in relation to incident heart failure in the population-based Rotterdam Study. METHODS AND RESULTS: The analysis comprised 5299 subjects (41% men, age approximately 68 years) free from heart failure for whom dietary data were available. During 11.4 years of follow-up, 669 subjects developed heart failure. The relative risk (RR) of heart failure in the top vs. bottom quintile of EPA plus DHA intake was 0.89 (95% CI 0.69-1.14), after adjustment for lifestyle and dietary factors. For fish intakes > or = 20 g/day, the RR was 0.96 (0.78-1.18) compared with no fish intake. In sex-specific analysis, a high EPA plus DHA intake tended to be protective in women (RR = 0.75, 0.54-1.04) but not in men (RR = 1.00, 0.73-1.36). An inverse association for EPA plus DHA was also observed in diabetics (RR = 0.58, 0.32-1.06), which was borderline statistically significant. CONCLUSION: Our findings do not support a major role for fish intake in the prevention of heart failure. The potentially protective effect of EPA plus DHA in diabetic patients, however, warrants further investigation.