INTRODUCTION: Despite current conventional treatments including steroids, immunomodulators, and anti-inflammatory medications, many patients with recurrent flares of ulcerative colitis (UC) often require more intensive therapy including biologics, and even colectomy. A dysregulated immune response to intestinal mucosal hypoxia contributes to the pathogenesis of UC, resulting in a loss of epithelial barrier function, translocation of luminal antigens into mucosa, and subsequent inflammation, making targeting of hypoxia-sensitive pathways a promising therapeutic approach.1 Recent literature supports the therapeutic potential of adjunctive hyperbaric oxygen therapy (HBOT).2 We present a case in which HBOT was used to help induce remission in an inpatient with severe refractory UC. CASE DESCRIPTION/METHODS: A 32-year-old male with a history of severe, chronic pan-UC presented to our clinic with a severe flare. Previously, he had a lack of response on multiple drug regimens to include azathioprine and infliximab. He was actively on vedolizumab therapy with minimal clinical and endoscopic response despite adequate levels and no antibodies detected. After missing an infusion, he developed an acute flare; presenting with >7 bloody bowel movements daily, fatigue, tenesmus, and a 20lb weight loss. Colonoscopy on hospital day (HD) 1 showed Mayo 3 pancolitis with biopsies negative for CMV. He received daily methylprednisolone and repeat induction dosing of vedolizumab with minimal clinical response. He subsequently underwent three 30-minute sessions of HBOT with significant symptomatic improvement. Tenesmus resolved and stools became non-bloody and semi-formed by the day of discharge. At 3-month follow-up, he remained in clinical remission with a normal fecal calprotectin on vedolizumab. DISCUSSION: Twenty-five percent of patients with UC will develop severe, acute exacerbations of disease during their lifetime. Despite advancements in treatment, half of these patients will fail subsequent medical rescue therapy, and an additional half of those will require colectomy within five years.3 Hyperbaric oxygen therapy is safe, well tolerated, and may play a role in inducing remission.4 The ability to increase tissue oxygen delivery to inflamed bowel to ultimately revert inflammatory pathways and promote healing may help avoid colectomy in select patients.5 Further research and ongoing clinical trials are necessary to investigate and better define the role of HBOT in inflammatory bowel disease.Figure 1.: Endoscopic view of the distal colon showing severe inflammation.Figure 2.: Endoscopic view of the sigmoid colon showing severe inflammation.Figure 3.: Endoscopic view of the rectum showing severe inflammation.