BACKGROUND: Musculoskeletal manifestations occur in half of the patients with inflammatory bowel disease (IBD) and contribute to a reduced quality of life (QoL) and increased work disability. We aimed to evaluate the natural disease course, characteristics, and risk factors of musculoskeletal manifestations in patients with IBD. METHODS: We performed a prospective longitudinal cohort study in patients with IBD with and without musculoskeletal manifestations with a 1-year follow-up. Primary outcome was the proportion of patients with resolution of musculoskeletal manifestations. Secondary outcomes included the proportion of patients with IBD that developed new musculoskeletal manifestations during follow-up; the correlation among IBD activity, baseline characteristics, and musculoskeletal disease course; and the difference in QoL between patients with and without musculoskeletal manifestations. RESULTS: In total, 243 patients with IBD were included (124 with and 119 without musculoskeletal manifestations). In the majority of patients (62.2%), musculoskeletal manifestations were of noninflammatory nature. Overall, peripheral and axial manifestations were persistent in 85.7 and 44.6% at 1 year, respectively. The QoL at baseline and at 1 year was lower in the group with musculoskeletal manifestations compared with patients without these manifestations. Female sex and age above 40 were associated with the presence of musculoskeletal manifestations. CONCLUSION: Musculoskeletal manifestations in patients with IBD are mostly noninflammatory disorders, persist at 1 year of follow-up, and occur more frequently in patients of age above 40 and female sex. Overall, patients with musculoskeletal manifestations have lower QoL compared with patients without musculoskeletal manifestations.