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The potential beneficial effects of fish consumption on heart failure (HF) may be modified by major food contaminants in fish. Polychlorinated biphenyls (PCBs) in particular, have been associated with well-established risk factors of HF such as coronary heart disease, hypertension, and diabetes. Likewise, experimental and cross-sectional studies in humans suggest that PCB exposure may be involved in the development of HF. We aimed to assess the association of both dietary PCB and long-chain omega-3 fish fatty acids exposures with risk of HF in two large population-based prospective cohorts.We used the Swedish Mammography Cohort and the Cohort of Swedish Men, comprising 32,867 women and 36,545 men, free of cancer, heart failure, myocardial infarction and diabetes at baseline in 1997. A questionnaire on diet (96-food items) and lifestyle factors was completed at baseline. We calculated validated estimates of dietary PCB exposure and intake of long-chain omega-3 fish fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)]. First incident cases of HF were ascertained through computerized linkage to the National Patient Register and the Cause of Death Register, defined as hospitalizations for (listed as the primary diagnosis) or death from HF. We use multivariable-adjusted Cox regression to estimate hazard ratio (HR) and its 95% confidence interval (CI), by quintiles of dietary PCB and EPA/DHA and controlling for known HF risk factors.During an average of 12 years of follow-up, 1,263 and 1,606 first incident cases of HF were ascertained in women and men, respectively. In multivariable-adjusted models, we observed no association between dietary PCB exposure or EPA/DHA intake and risk of HF. However, after additional mutual adjustments for PCBs and EPA/DHA, HRs for dietary PCB exposure were 1.60 (95% CI, 1.08-2.38) among women and 1.40 (95% CI, 0.97-2.02) among men, comparing extreme quintiles. The corresponding HRs for EPA/DHA intake were 0.62 (95% CI, 0.42-0.92) and 0.79 (95% CI, 0.55-1.13), respectively.Dietary exposure to PCBs was associated with an increased risk of HF in women, while EPA/DHA intake was associated with a lower risk of HF. Results for men was less evident but showed a similar trend. The results provide important information regarding the risk-benefit analysis of fish consumption, especially in cardiovascular disease prevention.