Abstract Background The optimal dosing strategy of infliximab (IFX) in Acute Severe Ulcerative Colitis (ASUC) is unknown. We compared intensified and standard dose IFX strategies in ASUC. Methods In this open-label randomised trial (NCT02770040), patients from 13 Australian centres with intravenous steroid-refractory ASUC were randomised to receive a first dose of 10mg/kg or 5mg/kg IFX in a 1:2 ratio. Patients in the 10mg/kg group (intensified induction [II]) received a second dose at day 7 or earlier at time of non-response; all 5mg/kg patients were re-randomised 1:1 to standard (SI) or accelerated induction (AI), which produced three induction groups: II, SI and AI. SI patients received 5mg/kg at week 0, 2 and 6, with an extra 5mg/kg dose before day 7 if non-response. AI patients received 5mg/kg at week 0, 1 and 3, with the week 1 dose increased to 10mg/kg and given earlier if non-response. Primary outcome: clinical response by day 7 (reduction in Lichtiger score to <10, with decrease of ≥3 points and improvement in rectal bleeding and stool frequency to ≤4/day). Secondary outcomes compared induction regimens until month 3. Analysis was by intention to treat. Results Between July 2016 & September 2021, 138 patients were randomised; 46 received a first IFX dose of 10mg/kg and 92 received 5mg/kg. Primary outcome: day 7 clinical response was observed in 65% (30/46) of 10mg/kg vs 61% (56/92) of 5mg/kg patients (P=0.76). In the 5mg/kg group, the rate of day 7 response was numerically lower in those with albumin <25g/L vs ≥25g/L [47% (15/32) vs 68% (41/60), P=0.07]. No difference in clinical response was observed in the 10mg/kg group when stratified by albumin [64% (9/14) vs 66% (21/32) P>0.99]. There was no difference in time to clinical response, change in Lichtiger score or CRP from baseline to day 7. Two patients who received 10mg/kg IFX underwent colectomy in the first 7 days vs 0 in the 5mg/kg group (P=0.21). Comparison of induction regimens (II, SI & AI): no difference in clinical remission rates between weeks 2 and 6 were observed. AI and II groups had higher rates of combined clinical and biochemical remission compared to SI between weeks 2 and 6 (P=0.042). At 3 months, there was no difference in rates of endoscopic and steroid-free remission, as well as rates of colectomy (II 7%; SI 12%; AI 19%, P=0.20). Conclusion In steroid-refractory ASUC, a first dose of 10mg/kg or 5mg/kg IFX achieved similar clinical response rates by day 7. Patients receiving intensified or accelerated induction achieved clinical and biochemical remission earlier compared to standard induction; however, outcomes at three months were similar. Patients with a lower albumin may benefit from proactive intensified dosing strategies.