The authors examined the association of intakes of different types of fat and fatty acids with risk of colorectal cancer using data from the Women's Health Study, a randomized trial of low-dose aspirin and vitamin E carried out among 39,876 healthy US women aged >/=45 years. Among the 37,547 women eligible for the present study, 202 developed colorectal cancer during an average follow-up period of 8.7 years (1993-2003). Intakes of dietary fat and its food sources were assessed at baseline by food frequency questionnaire. Cox proportional hazards regression was used to estimate relative risks and 95% confidence intervals. Total fat intake was not related to colorectal cancer risk, nor were intakes of the different types of fat and major fatty acids. However, the authors observed a positive association between intake of fried foods away from home and colorectal cancer risk (highest quintile vs. lowest: relative risk = 1.86, 95% confidence interval: 1.09, 3.16; p for trend = 0.01). These prospective cohort data provide little support for an association between dietary fat and colorectal cancer risk. However, intake of fried foods and/or other factors related to their intake may be associated with colorectal cancer development. This finding warrants further examination.