Objective Diffuse mucosal inflammation in the duodenum, distinct from peptic ulcer disease, has been repeatedly reported in patients with ulcerative colitis (UC). The pathogenesis of this complication remains uncertain; however, colectomy for medically refractory UC appears to trigger duodenitis. Cases in which colectomy was performed for UC were analyzed to characterize UC-related duodenitis after colectomy. Methods A retrospective case-control study of UC-related duodenitis that developed after colectomy in medically refractory UC between January 2011 and June 2020 was conducted. UC-related duodenitis was diagnosed based on typical clinical, endoscopic, and histological findings, and no duodenitis was endoscopically defined by the normal duodenal mucosa. Clinical and laboratory data, disease severity, and medications used were collected and compared between the UC-related and non-duodenitis cases. Results Ten UC-related duodenitis and 35 non-duodenitis cases were identified among 45 patients with UC who underwent esophagogastroduodenoscopy after colectomy. Disease severity, defined by the C-reactive protein level and partial Mayo score prior to colectomy, was significantly higher in duodenitis patients than in non-duodenitis patients. In comparison to non-duodenitis patients, duodenitis patients more frequently received rescue therapies with calcineurin inhibitors or anti-TNF-α agents at the time of colectomy (100% vs. 65.7%). Conclusion Patients with UC with higher disease activity, especially those who require rescue therapies with calcineurin inhibitors and anti-TNF-α agents, may be prone to developing UC-related duodenitis after colectomy.