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Objective Medical rescue therapy (MRT) is effective in intravenous corticosteroid refractory acute severe ulcerative colitis (ASUC). Our aim was to identify predictors of response to MRT and avoid colectomy in the index admission or within 12 months.Methods Two cohorts were studied retrospectively. Analysis of 49 adults receiving MRT between 2015 and 2019 at two tertiary Australian hospitals was first performed. Clinical, endoscopic and laboratory data were collected. Response was defined as avoiding colectomy during the same admission. Univariable and multivariable logistic regression were employed to identify predictors of response. The predictors were validated in 88 patients receiving MRT between 2020 and 2023.Results In the development cohort, 40/49 (81.6%) patients responded to MRT. On multivariable analysis, Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score at admission (Coef −0.105 (−0.19 to –0.007), p=0.03) and C-reactive protein (CRP) on day 3 of post commencement of MRT (CRP-R+3) (Coef −0.004 (−0.0008 to −0.0004), p=0.03) identified response to MRT. All patients (n=17) with a UCEIS score <6 (UCEIS <6) and 100% (n=28) patients with a CRP-R+3 <22 mg/L responded to MRT. In the validation cohort, 82/88 (93.1%) patients responded to MRT; 90.5% (19/21) with UCEIS <6 and 100% (70/70) patients with CRP-R+3 <22 mg/L responded to MRT. At 12 months after hospitalisation for ASUC, in the development cohort, 16/17 (94%) patients with a UCEIS <6 and 23/28 (82.1%) patients with CRP-R+3 <22 mg/L avoided colectomy. In the validation cohort, 18/21 (85.7%) with UCEIS <6 and 64/70 (91.4%) patients with CRP-R +3 <22 mg/L avoided colectomy at 12 months.Conclusions UCEIS <6 and CRP-R+3 <22mg/L identify responders to MRT, and colectomy is extremely unlikely either on the index admission or within 12 months.