We examined the associations between changes in dietary inflammatory potential and risk of colorectal cancer (CRC) in 87,042 postmenopausal women recruited from 1993-1998 into the Women's Health Initiative. Food frequency questionnaire data were used to compute patterns of change in dietary inflammatory index (DII) scores and cumulative average DII scores over 3 years. Cox regression models were used to estimate hazard ratios for CRC risk. After a median 16.2 years follow-up, 1,038 CRC cases were diagnosed. DII changes were not substantially associated with overall CRC, but proximal colon cancer risk was higher in the pro-inflammatory change DII compared to the anti-inflammatory stable DII groups (hazard ratio = 1.32; 95% confidence interval: 1.01, 1.74). Among non-users of nonsteroidal anti-inflammatory drugs (NSAID) (Pinteraction = 0.055) the pro-inflammatory stable DII group was at increased risk of overall CRC and proximal colon cancer. Also among non-users of NSAID, risks of overall CRC, colon cancer, and proximal colon cancer were higher in the highest quintile compared to the lowest cumulative average DII quintile (65%, 61%, and 91% increased risk, respectively). Dietary changes towards, or a history of, pro-inflammatory diets are associated with an elevated risk of colon cancer, particularly for proximal colon cancer and among non-users of NSAID.