Only a few prospective studies have investigated flavonols as risk factors for cancer, none of which has included pancreatic cancer. The latter is usually fatal, rendering knowledge about prevention particularly important. The authors estimated intakes of three flavonols-quercetin, kaempferol, and myricetin-for 183,518 participants in the Multiethnic Cohort Study and examined associations with incidence of pancreatic cancer. Baseline data were collected in Hawaii and California in 1993-1996. Diet was assessed by using a quantitative food frequency questionnaire. During 8 years of follow-up, 529 cases of exocrine pancreatic cancer occurred. Multivariate Cox regression models were calculated to estimate relative risks. Intake of total flavonols was associated with a reduced pancreatic cancer risk (relative risk for the highest vs. lowest quintile = 0.77, 95% confidence interval: 0.58, 1.03; p trend = 0.046). Of the three individual flavonols, kaempferol was associated with the largest risk reduction (relative risk = 0.78, 95% confidence interval: 0.58, 1.05; p trend = 0.017). Total flavonols, quercetin, kaempferol, and myricetin were all associated with a significant inverse trend among current smokers (relative risks for the highest vs. lowest quartile = 0.41, 0.55, 0.27, 0.55, respectively) but not never or former smokers. This study provides evidence for a preventive effect of flavonols on pancreatic cancer, particularly for current smokers.