Most previous prospective studies in Western countries found no association between consumption of fish and omega-3s and pancreatic cancer risk. However, prospective evidence is still lacking among populations who have a relatively higher fish consumption. We investigated the association between fish and n–3 PUFA consumption and pancreatic cancer risk in a population-based, prospective study in Japanese men and women. We analyzed data on 82,024 eligible participants aged 45–74 y without a history of cancer. Participants were followed through 2010. During 1,068,774 person-years of follow-up, 449 newly diagnosed pancreatic cancers were identified. We found an inverse association of omega-3 consumption with pancreatic cancer risk. We conclude high omega–3 consumption was associated with a lower risk of pancreatic cancer in a population with a large variation in fish consumption.