BACKGROUND/OBJECTIVES: To examine associations between food patterns, constructed with cluster analysis, and colorectal cancer incidence within the National Institutes of Health-AARP Diet and Health Study. SUBJECTS/METHODS: A prospective cohort, aged 50-71 years at baseline in 1995-1996, followed until the end of 2000. Food patterns were constructed, separately in men (n=293,576) and women (n=198,730), with 181 food variables (daily intake frequency per 1000 kcal) from a food frequency questionnaire. Four large clusters were identified in men and three in women. Cox proportional hazards regression examined associations between patterns and cancer incidence. RESULTS: In men, a vegetable and fruit pattern was associated with reduced colorectal cancer incidence (multivariate hazard ratio, HR: 0.85; 95% confidence interval, CI: 0.76, 0.94), when compared to less salutary food choices. Both the vegetable and fruit pattern and a fat-reduced foods pattern were associated with reduced rectal cancer incidence in men. In women, a similar vegetable and fruit pattern was associated with colorectal cancer protection (age-adjusted HR: 0.82; 95% CI: 0.70, 0.95), but the association was not statistically significant in multivariate analysis. CONCLUSIONS: These results, together with findings from previous studies support the hypothesis that micronutrient dense, low-fat, high-fiber food patterns protect against colorectal cancer.