Dietary flavonoids can inhibit cancer development by protecting tissues against free oxygen radicals and inhibiting cell proliferation, but observational studies of flavonoid intake and colorectal cancer incidence are sparse. The authors prospectively evaluated the association between intake of flavonoids and colorectal cancer incidence in 71,976 women from the Nurses' Health Study and 35,425 men from the Health Professionals Follow-Up Study. Dietary intake was assessed in 1990, 1994, and 1998 by means of a food frequency questionnaire. The authors used Cox proportional hazards models with time-varying variables to estimate relative risks of colorectal cancer. Between 1990 and 2000, the authors documented 878 incident cases of colorectal cancer (498 in women and 380 in men). Total flavonoid intake was not inversely associated with colorectal cancer risk among women and men combined. The combined relative risk for the highest quintile of total flavonoid intake compared with the lowest was 1.19 (95% confidence interval: 0.94, 1.49; p for trend = 0.15). Higher intakes of individual flavonols, including quercetin, myricetin, and kaempferol, were also not related to a lower risk of colorectal cancer. These data provide little support for the hypothesis of an association between flavonoid intake and colorectal cancer risk, at least within the ranges of intakes consumed in the populations studied.