BACKGROUND: Requirement for hospitalization in ulcerative colitis (UC) is a marker of severity of disease. However, the paradigm of when to escalate therapy in such patients and the benefits of early immunomodulator initiation is less well established. AIM: To examine the benefits of early therapy escalation in immunosuppression-naive patients hospitalized with severe ulcerative colitis responsive to steroids. METHODS: We identified hospitalized UC patients who were immunosuppression naive at index hospitalization and responded to intravenous steroids, not requiring medical or surgical rescue therapy. The 'therapy escalated' group comprised of those who were initiated on immunomodulators within 3 months of hospitalization. The need for colectomy at 12 months was compared to the 'not escalated' group who remained on non-immunosuppressive therapy. RESULTS: Among 133 immunosuppressive naive patients hospitalized for ulcerative colitis, 13 (9.8%) who responded to intravenous steroids and did not require rescue therapy underwent colectomy by 1 year. Among 123 patients who escalated to either immunomodulators (n = 46, 37%) or remained on non-immunosuppressive therapy (92% on 5-ASA), there was no difference in the need for colectomy at 1 year (10.8 vs. 7.8%; multivariate OR 1.29, 95% CI 0.35-4.74). There was also no difference in the time to colectomy between the two groups (p = 0.55). CONCLUSION: Immunosuppression-naive ASUC patients who respond to intravenous steroids remain at risk for colectomy. Immunomodulator initiation by 3 months did not reduce risk of colectomy at 1 year. There is an important need for prospective studies identifying thresholds for therapy escalation in UC.