Hospitalized patients with acute severe ulcerative colitis (ASUC) often require surgery. Although the tumor necrosis factor antagonist infliximab is an effective salvage therapy to prevent colectomy in patients with ASUC, optimal dosing is unclear. Calculated infliximab clearance has been associated important outcomes in patients with ulcerative colitis, but its utility in patients with ASUC has not been established. We assessed the relationship between calculated baseline infliximab clearance prior to infliximab salvage therapy and requirement for colectomy in patients hospitalized for ASUC.We obtained data from hospitalized patients with ASUC who initiated infliximab therapy. We then calculated baseline infliximab drug clearance in these patients based on an existing formula. The primary aim was to compare clearance between patients who required colectomy 6 months later and patients who did not require colectomy. Receiver operating characteristic curve analyses evaluated clearance thresholds for colectomy. Multivariable logistic regression analysis evaluated factors associated with colectomy.In 39 patients with ASUC, median baseline calculated clearance was higher in patients requiring colectomy at 6 months than in patients without colectomy (0.733 vs 0.569 L/day; P=.005). An infliximab clearance threshold of 0.627 L/day identified patients who required colectomy with 80.0% sensitivity and 82.8% specificity (area under the curve, 0.80). A higher proportion of patients with infliximab clearance of 0.627L/day or more underwent colectomy within 6 months (61.5%) than patients with lower infliximab clearance values (7.7%) (P=.001). Multivariable analysis identified baseline infliximab clearance as the only factor associated with colectomy. Infliximab dose in hospital was higher in patients who required colectomy. Results were similar at 30 days and 1 y.In patients hospitalized with ASUC, higher values of calculated infliximab clearance before infliximab administration is associated with higher rates of colectomy. Although patients who required colectomies received higher doses, data on infliximab concentrations are lacking. Infliximab pharmacokinetic models are needed for patients with ASUC, to allow comparative trials on clearance-based vs standard dosing.