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Intakes of whole grains and cereal fiber have been inversely associated with the risk of chronic diseases; however, their relation with total and disease-specific mortality remain unclear. We aimed to prospectively assess the association of whole grains and cereal fiber intake with all causes and cause-specific mortality.The study included 367,442 participants from the prospective NIH-AARP Diet and Health Study (enrolled in 1995 and followed through 2009). Participants with cancer, heart disease, stroke, diabetes, and self-reported end-stage renal disease at baseline were excluded.Over an average of 14 years of follow-up, a total of 46,067 deaths were documented. Consumption of whole grains were inversely associated with risk of all-cause mortality and death from cancer, cardiovascular disease (CVD), diabetes, respiratory disease, infections, and other causes. In multivariable models, as compared with individuals with the lowest intakes, those in the highest intake of whole grains had a 17% (95% CI, 14-19%) lower risk of all-cause mortality and 11-48% lower risk of disease-specific mortality (all P for trend0.023); those in the highest intake of cereal fiber had a 19% (95% CI, 16-21%) lower risk of all-cause mortality and 15-34% lower risk of disease-specific mortality (all P for trend0.005). When cereal fiber was further adjusted, the associations of whole grains with death from CVD, respiratory disease and infections became not significant; the associations with all-cause mortality and death from cancer and diabetes were attenuated but remained significant (P for trend0.029).Consumption of whole grains and cereal fiber was inversely associated with reduced total and cause-specific mortality. Our data suggest cereal fiber is one potentially protective component.