Abstract Background Tofacitinib is a rapidly acting Janus kinase (JAK) inhibitor with increasing evidence of effectiveness in patients with acute severe ulcerative colitis (ASUC). However, there are scarce prospective data analyzing the efficacy and rapidity of action in hospitalized ASUC. Methods The TRIUMPH study is a prospective open-label interventional trial of tofacitinib in hospitalized patients with ASUC conducted in 5 hospitals across Canada (Clinicaltrials.gov: NCT04925973). Eligible participants included biologic-naïve and experienced patients with ASUC refractory to 3 days of intravenous (IV) corticosteroids (Modified Truelove-Witts Severity Index [MTWSI] > 10 despite steroids). Participants were treated with tofacitinib 10 mg twice daily and assessed daily while in hospital. The primary outcome was day 7 clinical response (MTWSI reduction of > 3 from baseline and ≤ 10). Results Among 24 subjects, 33.3% (8/24) had previous anti-TNF failure. Day 7 clinical response was achieved in 58.3% (14/24). The mean number of days to achieve clinical response was 2.4 (SD 1.3). Marked reduction in C-reactive protein was observed in responders within the first two days after tofacitinib initiation compared to nonresponders. Colectomy occurred in 25% (6/24) by 6 months, with no additional colectomy beyond this time point. Five participants reported a total of 13 adverse events. Conclusions Tofacitinib is an effective rescue therapy in hospitalized patients with steroid-refractory ASUC. Randomized controlled trials are warranted to compare JAK inhibitors with other rescue therapies, including infliximab in steroid-refractory ASUC (Clinicaltrials.gov: NCT04925973).