Objectives:Ulcerative colitis (UC) is a chronic inflammatory disease usually responding well to anti-inflammatory drugs but many patients will still need colectomy. Appendectomy is associated with a lower risk of later developing UC. We aimed to assess the longitudinal relationship between appendectomy, appendicitis, and disease course in UC patients.Methods:A national cohort of UC patients with a diagnosis in 1964–2010 was identified from the Swedish National Patient Register that also provided information regarding appendicitis and/or appendectomy before or after the UC diagnosis. The risk for colectomy and UC-related hospital admissions was evaluated.Results:Among 63,711 UC patients, 2,143 had appendectomy and 7,690 underwent colectomy. Appendectomy for appendicitis before 20 years of age and for non-appendicitis at all ages before UC diagnosis was associated with a lower risk of colectomy (hazard ratio (HR) 0.44, 0.27–0.72 and HR 0.62, 0.43–0.90, respectively), and fewer hospital admissions (incidence rate ratio (IRR) 0.68, 95% confidence interval (CI) 0.64–0.73 and IRR 0.54, 0.47–0.63, respectively). Appendectomy for appendicitis after the UC diagnosis was associated with a higher risk of colectomy (HR 1.56, 1.20–2.03), whereas no such association was found for other pathology (HR 1.40, 0.79–2.47).Conclusions:Appendectomy early in life and before developing UC is associated with a lower risk of colectomy as well as UC-related hospital admissions. Appendectomy for appendicitis after established UC appears associated with a worse disease course, with an increased rate of subsequent colectomy.