BACKGROUND Recent findings have cast doubt on the hypothesis that high intakes of fruit and vegetables are associated with a reduced risk of colorectal cancer. OBJECTIVE In a large prospective cohort of women, we examined the association between fruit and vegetable intakes and colorectal cancer. METHODS Between 1987 and 1989, 45490 women with no history of colorectal cancer satisfactorily completed a 62-item Block-National Cancer Institute food-frequency questionnaire. During 386142 person-years of follow-up, 314 women reported incident colorectal cancer, searches of the National Death Index identified an additional 106 colorectal cancers, and a match with state registries identified another 65 colorectal cancers for a total of 485 cases. We used Cox proportional hazards regression analysis to estimate the relative risks (RRs) and 95% CIs in both energy-adjusted and fully adjusted models. RESULTS In models using the multivariate nutrient-density model of energy adjustment, RRs for increasing quintile of fruit consumption indicated no significant association with colorectal cancer [RR (95% CI)]: 1.00 (reference), 0.94 (0.70, 1.26), 0.85 (0.63, 1.15), 1.07 (0.81, 1.42), and 1.09 (0.82, 1.44). For vegetable consumption, there was also no significant association in the multivariate nutrient-density model with increasing quintiles of consumption: 1.00 (reference), 0.77 (0.58, 1.02), 0.83 (0.63, 1.10), 0.90 (0.69, 1.19), and 0.92 (0.70, 1.22). Additionally, 3 alternative models of energy adjustment showed no significant association between increases in vegetable intake and the risk of colorectal cancer. CONCLUSIONS Although the limitations of our study design and data merit consideration, this investigation provides little evidence of an association between fruit and vegetable intakes and colorectal cancer.