Most data suggest that the regular use of aspirin reduces the risk of colorectal cancer, but some apparently conflicting evidence exists. The effects of the dose and the duration of aspirin consumption on the risk of colorectal cancer are not well understood. We determined rates of colorectal cancer according to the number of consecutive years of regular aspirin use (defined as two or more tablets per week) among women in the Nurses' Health Study who reported regular aspirin use on three consecutive questionnaires (1980, 1982, and 1984) and compared the rates in this group with the rates among women who said they did not use aspirin. Cases of cancer occurring from 1984 through 1992 (the eight years after the 1984 questionnaire) were included. From 1984 through 1992, we documented 331 new cases of colorectal cancer during 551,651 person-years of follow-up. Women who consistently took two or more aspirin tablets per week had no appreciable reduction in the risk of colorectal cancer as compared with nonusers after four years (relative risk, 1.06; 95 percent confidence interval, 0.78 to 1.45) or after five to nine years (relative risk, 0.84; 95 percent confidence interval, 0.55 to 1.28). There was a slight reduction in risk among women who took aspirin for 10 to 19 years, but it was not statistically significant (relative risk, 0.70; 95 percent confidence interval, 0.41 to 1.20). However, there was a statistically significant reduction after 20 years of consistent use of aspirin (relative risk, 0.56; 95 percent confidence interval, 0.36 to 0.90; P for trend = 0.008). The maximal reduction in risk was observed among women who took four to six tablets per week; higher doses had a similar apparent benefit. Controlling for risk factors for colorectal cancer, including diet, did not change the results, and the earlier diagnosis and removal of colorectal adenomas among aspirin users did not account for the results. Regular aspirin use, at doses similar to those recommended for the prevention of cardiovascular disease, substantially reduces the risk of colorectal cancer. However, this benefit may not be evident until after at least a decade of regular aspirin consumption.