BACKGROUND: Clostridioides difficile infection (CDI) and acute severe ulcerative colitis (ASUC) are both independently associated with poor outcome. The impact of CDI on the outcome of severe flare of ulcerative colitis is not studied. In the current study, we assess the impact of CDI on the outcome of ASUC. METHODS: Data of ASUC patients were collected from January 2022 to July 2024. Parameters included were demographic profile, disease characteristics, biochemical investigations, and stool C. difficile toxin A/B (CDTA). Patients were categorized into ASUC-CDI and ASUC groups. Primary outcomes were need of rescue therapy, colectomy, and mortality during index admission. Six-month outcomes were flare of disease, colectomy, and mortality. RESULTS: Of the 117 patients included, 91 (77.8%) patients were in the ASUC group and 26 (22.2%) in the ASUC-CDI group. Baseline parameters were similar between the 2 groups. Overall, 86 (73.5%) patients responded to corticosteroid therapy. Need of rescue therapy (24.2% vs. 33.6%, P=0.287), colectomy (3.3% vs. 11.5%, P=0.093), and mortality (1.1% vs. 3.8%, P=0.345) rates were comparable between the ASUC and ASUC-CDI groups. Six-month colectomy (4.4% vs. 15.4%) and mortality (1.1% vs. 7.7%) rates were numerically higher in the ASUC-CDI group, though statistically nonsignificant. CONCLUSION: The immediate and short-term outcome of patients with acute severe ulcerative colitis in the presence of C. difficile infection is determined by the severity of ulcerative colitis flare.