Diet and inflammation have been suggested to be important risk factors for ulcerative colitis (UC). In this case-control study conducted in Iran, we examined the ability of the dietary inflammatory index (DII) to predict UC. This study included 62 UC cases and 124 controls hospitalized for acute non-neoplastic diseases. The DII was computed based on dietary intake assessed by a previously validated food frequency questionnaire. Multivariable logistic regression models were used to estimate odds ratios (ORs) and the DII was analyzed as both continuous and as tertiles. Energy was adjusted using the residual method. Subjects with higher DII scores (i.e., with a more pro-inflammatory diet) had a higher risk of UC, with the DII being used as both a continuous variable (OR(continuous) 1.55, 95% confidence interval (CI) 1.04-2.32; one unit increase corresponding to ≈8% of its range in the current study) and as tertiles (OR(tertile3vstertile1) 2.58, 95% CI 1.03-6.48, P(trend)| = |0.04). These results indicate that a pro-inflammatory diet is associated with increased risk of UC.