The prevalence of immune-related systemic manifestations associated with inflammatory bowel disease varies widely in different studies. This prospective hospital study examines the prevalence and clinical aspects of these manifestations. A total of 792 patients, 449 with Crohn's disease and 343 with ulcerative colitis, were followed up from diagnosis to 20 years. Data related to systemic manifestations and to the extent and severity of intestinal lesions were obtained at diagnosis and during follow-up. Extraintestinal manifestations related to the activity of intestinal inflammation appeared at least once in 25.8% of the patients. The cumulative probability of extraintestinal manifestations increased from 12%-30% during the 20-year follow-up; it was significantly higher in patients with Crohn's disease (p < 0.01). Arthritis (p < 0.001) and erythema nodosum (p < 0.01) were more frequent in Crohn's disease. A significant positive association of arthritis with skin, eye, and mouth complications was observed (p < 0.001). Bowel-related systemic manifestations appeared frequently together in the same patient (p < 0.001). Patients with any of these manifestations ran a higher risk of developing another one. Autoimmune manifestations were associated with both Crohn's disease and ulcerative colitis.