Abstract Background Ulcerative Colitis (UC) is a chronic inflammatory condition, which significantly impacts patients’ health-related quality of life and burdens healthcare budgets. Our objective was to provide an overview of the healthcare resource use (HCRU) for the treatment of moderate to severe UC in Germany. Methods A retrospective analysis was conducted using claims data from a German sickness fund (AOK PLUS). Patients were included if they had ≥2 outpatient diagnoses in different quarters and/or one inpatient UC diagnosis (ICD-10: K51), were aged ≥18 years and initiated an advanced therapy (anti-TNFs, vedolizumab, tofacitinib) between 01/01/2015-30/06/2019. HCRU associated with UC treatment was assessed in terms of outpatient visits, work-related sick leave days, and UC caused hospitalizations. Direct UC-related costs (inpatient, outpatient and medication costs based on pharmacy sales price at prescription date) were calculated from the perspective of the German statutory health insurance. All patients were followed from the start of treatment until the end of the study period, or loss to follow-up. In case of treatment discontinuation or change of index therapy, patient follow-up was censored 90 days after the last prescription of index therapy. UC-related HCRU and cost were reported per observable patient-year (PY) and stratified according to prior use of advanced therapies (naïve vs. experienced). Results 574 patients were included (adalimumab: 230, infliximab: 172, golimumab: 56, vedolizumab: 113, tofacitinib: 3). Mean age was 41.9 years; 53.5% were female. On average, 2.5 outpatient visits per PY were billed by general practitioners and 1.4 by gastroenterologists. 27.0% of patients had at least one UC-related hospitalization (mean length of stay: 11.2 days). The mean number of documented UC-related sick leave days amounted to 13.1 per PY. HCRU was similar in therapy-naïve vs. experienced patients (Table 1). Inpatient costs for any cause amounted on average to €4,522/PY, with UC accounting for €3,190/PY (70.5%). Total UC costs amounted to €34.068/PY (Table 2). Expenses for prescribed UC-related drugs amounted to €28,885/PY (95.6% of total drug costs), and outpatient treatment to €511/PY with only €123/PY for Gastroenterologists’ visits (0.4% of total UC-costs/PY). In addition, indirect cost resulting from sick leave due to UC were estimated at €2,979/PY. Conclusion Our study indicates a high economic burden in UC patients who initiated treatment with advanced therapies. UC-related medication was identified as the main cost driver. Furthermore, a substantial proportion of UC patients required hospitalization in the first 12 months after starting new advanced therapy.