Background: Colectomy rates in acute severe ulcerative colitis (ASUC) patients have declined over the last 25 years. Objective predictors of non-response to IV corticosteroids (IVCS) in ASUC can further improve outcomes. Our aim was to develop and validate predictors of IVCS non-response in ASUC patients in the biologic era. Methods: Consecutive patients with ASUC satisfying Truelove and Witts’ criteria hospitalised at two tertiary IBD centres in Australia between 2013-2020 were included. Primary outcome was steroid non-response requiring medical or surgical rescue therapy. UCEIS was scored on flexible sigmoidoscopy performed within 24-48 hours of admission. Development cohort comprised 112 episodes of ASUC between 2013 and 2017, and the validation cohort comprised 114 episodes of ASUC between 2018-2020. Results: In the development cohort, 52 (46.4%) episodes were steroid non-responders and 18 (16%) episodes underwent colectomy during the same admission. On multi-variable analysis, predictors of non-response to IVCS were UCEIS score [OR 2.45 (1.65-3.63, p <0.001)] and serum albumin day 3 after admission [OR 0.83 (0.76-0.90), p <0.001]. A score was developed allocating 1 point to each variable (UCEIS ≥ 7 and day 3 serum albumin ≤ 25 mg/L) For predicting steroid non-response, the score had OR 6.31 (3.11- 12.79), p <0.001, AUROC 0.763 (0.676-0.849), score of 2 points had a sensitivity of 26%, specificity 100%, PPV 100, NPV 59.5%; for same admission colectomy OR 20.58 (6.16-68.6), p <0.001, AUROC 0.905 (0.846-0.964). In the validation cohort, 52 (45.6%) episodes were steroid non-responders and 7 (6.1%) episodes underwent colectomy during the same admission. For predicting steroid non-response, the score had OR 4.26 (2.07-8.76), p <0.001, AUROC 0.684 (0.593-0.776), score of 2 points had sensitivity 13%, specificity 100%, PPV 100%, NPV 57%; for same admission colectomy OR 5.42 (2.44-12.05), p <0.001, AUROC 0.83 (0.753-0.907). Conclusion: In the biologic era, UCEIS score and serum albumin on day 3 of admission are predictors of steroid non-response in patients with ASUC. We have developed and validated a score comprising UCEIS ≥ 7 and day 3 serum albumin ≤ 25mg/L. A score of 2 has a specificity of 100% and PPV 100% for predicting non-response to IVCS.