The purpose of this study was to test the hypothesis that aspirin use is associated with a decreased risk of incident colorectal cancer. From the Women’s Health Initiative, 91,574 participants between the ages of 50 and 79 years at baseline in 1993-1998 provided details on aspirin use via interview using a standardized questionnaire and were subsequently followed annually for incident colorectal cancer during a period of over 6 years. For those persons who reported aspirin use, the type of compound, dose, and duration of use were recorded. Medical histories suggestive of colorectal cancers at the annual update were verified by medical record and pathology report review by trained local physician adjudicators. There were 631 confirmed cases of invasive cancer of the colon or rectum. There was no significant association between any aspirin use and risk for incident colorectal cancer (hazard ratio = 0.96, 95% confidence interval: 0.8, 1.2). Moreover, with no aspirin use as the referent category, there were no significant associations for duration of aspirin intake by category (< 1, 1- < 2, 2- < 3, 3- < 4, 4- < 5, and > or = 5 years) or for daily dosage by category (< 165, 165- < 300, 300- < 495, or > or = 495 mg).