The associations of types of fish and fish preparation methods with pancreatic cancer risk remain unknown. The authors conducted a prospective cohort study in western Washington State among 66,616 adults, aged 50-76 years, who participated in the VITamins And Lifestyle cohort study. Diet was assessed by a food frequency questionnaire. Pancreatic cancer cases were identified by linkage to the Surveillance, Epidemiology, and End Results cancer registry. During an average follow-up of 6.8 years, 151 participants developed pancreatic cancer (adenocarcinoma). Long-chain (n-3) polyunsaturated fatty acids (LC-PUFAs) and nonfried fish intake were inversely associated with pancreatic cancer incidence. When the highest and lowest tertiles of exposure were compared, the multivariable-adjusted hazard ratio of pancreatic cancer was 0.62 (95% confidence interval: 0.40, 0.98) (P(trend) = 0.08) for LC-PUFAs and 0.55 (95% confidence interval: 0.34, 0.88) (P(trend) = 0.045) for nonfried fish. Docosahexaenoic acid showed a greater inverse association with pancreatic cancer than eicosapentaenoic acid. No statistically significant associations were observed with fried fish and shellfish consumption. The potential health impact of fish consumption may depend on the types of fish consumed and fish preparation methods. LC-PUFAs, particularly docosahexaenoic acid, and nonfried fish, but not shellfish or fried fish, may be beneficial in the primary prevention of pancreatic cancer.