INTRODUCTION: Diet can impact the clinical course of Crohn's disease (CD). However, the importance of food processing level is uncertain. We aimed to evaluate whether ultra-processed foods (UPFs) are associated with an increased risk of relapse among patients with CD in clinical remission. METHODS: In this prospective cohort study, adult patients with CD in clinical remission were followed for 1 year or until clinical relapse, as assessed by the Harvey Bradshaw index. Dietary intake was assessed using a food frequency questionnaire and a dedicated validated processed food questionnaire to evaluate UPF consumption. Multivariable Cox proportional hazard models were used to estimate the adjusted hazard ratio of disease relapse according to high or low UPF consumption. RESULTS: A total of 111 patients with CD (mean age 37.9 +/- 14.0 years) in clinical remission were followed. Over a median period of 12 months [interquartile range, 8-12], 24 patients (21.6%) experienced clinical relapse. Fecal calprotectin levels were increased at the relapse visit compared to baseline (193.0 mug/g [114.0-807.0] and 79.0 mug/g [17.0-274.5], respectively, p = 0.002). A higher intake of UPFs was associated with an increased risk of CD relapse (HR = 3.86; 95% CI 1.30-11.47). Ultra-processed breads and pastries, as well as oils and spreads, were the UPF subgroups with the strongest positive associations (HR = 3.27; 95% CI 1.26-8.45 and HR = 2.76; 95% CI 1.02-7.45, respectively). CONCLUSION: UPF consumption is associated with an increased risk of relapse in patients with CD in remission. This study, along with future research, can contribute to establishing nutritional guidelines aimed at reducing UPF consumption in this population.