BACKGROUND: Whether the intake of dietary fiber can protect against colorectal cancer is a long-standing question of considerable public health import, but the epidemiologic evidence has been inconsistent.OBJECTIVE: The objective was to investigate the relation between dietary fiber and whole-grain food intakes and invasive colorectal cancer in the prospective National Institutes of Health-AARP Diet and Health Study.DESIGN: The analytic cohort consisted of 291 988 men and 197 623 women aged 50-71 y. Diet was assessed with a self-administered food-frequency questionnaire at baseline in 1995-1996; 2974 incident colorectal cancer cases were identified during 5 y of follow-up. The Cox proportional hazards model was used to estimate the relative risks (RRs) and 95% CIs.RESULTS: Total dietary fiber intake was not associated with colorectal cancer. The multivariate RR for the highest compared with the lowest intake quintile (RR(Q5-Q1)) was 0.99 (95% CI: 0.85, 1.15; P for trend = 0.96). In analyses of fiber from different food sources, only fiber from grains was associated with a lower risk of colorectal cancer (multivariate RR(Q5-Q1): 0.86; 95% CI: 0.76, 0.98; P for trend = 0.01). Whole-grain intake was inversely associated with colorectal cancer risk: the multivariate RR(Q5-Q1) was 0.79 (95% CI: 0.70, 0.89) for the whole cohort (P for trend < 0.001). The association with whole grain was stronger for rectal than for colon cancer.CONCLUSIONS: In this large prospective cohort study, total dietary fiber intake was not associated with colorectal cancer risk, whereas whole-grain consumption was associated with a modest reduced risk.