Background: Colorectal cancer, the third most common cancer in the United States, has a natural history that usually encompasses several decades. Dietary components have been implicated in the etiology of colorectal cancer, perhaps through their effect on inflammation. Methods: We examined the ability of the dietary inflammatory index (DII) to predict colorectal cancer in the Iowa Women's Health Study. The DII was computed based on dietary intake assessed by a 121-item food frequency questionnaire in this cohort of 34,703 women, ages 55 to 69 years, free of any self-reported prior malignancy at enrollment in 1986. Incident colorectal cancer cases were identified through linkage with the State Health Registry of Iowa (a Surveillance, Epidemiology, and End Results program member). Cox proportional hazards regression was used to estimate HRs. Through the end of 2010, 1,636 incident colorectal cancers were identified, including 1,329 colon and 325 rectal cancers. Results: Multivariable analysis, adjusting for body mass index, smoking status, pack-years of smoking, hormone replacement therapy, education, diabetes, and total energy intake, revealed positive associations between higher DII and colorectal cancer risk [HR for DIIcontinuous: 1.07 per unit increase in DII (corresponding to 0.5 SD unit increase); 95% confidence interval (CI), 1.01-1.13; HR for DII quintiles: Q5 vs. Q1 = 1.20; 95% CI, 1.01-1.43]. HRs for DII were similar for colon cancer and rectal cancer, though not statistically significant for rectal cancer. Conclusions: These results indicate that a proinflammatory diet, as indicated by higher DII scores, was associated with higher risk of developing colorectal cancer. Impact: Proinflammatory diets are associated with increased risk of colorectal cancer.