Hyperbaric oxygen (HBO2) treatment is used across a range of medical specialties for a variety of applications, particularly where hypoxia and inflammation are important contributors. HBO2 may be useful for new indications not currently approved by the Undersea and Hyperbaric Medical Society (UHMS) because of its hypoxia-relieving and anti-inflammatory effects. Identifying these new applications for HBO2 is difficult because individual centers may only treat a few cases and not track outcomes consistently. The web-based International Multicenter Registry for Hyperbaric Oxygen Therapy captures prospective outcomes data for patients treated with hyperbaric oxygen (HBO2) therapy. These data can then be used to identify new potential applications for HBO2, which has relevance for a range of medical specialties. Although hyperbaric medicine has established indications, new ones continue to emerge. One objective of this registry study is to identify cases where HBO2 has been used for conditions falling outside of current UHMS-approved indications and present outcomes data for them. This is a descriptive study based on a web-based, multi-center, international, registry of patients treated with HBO2. Centers agree to collect data on all patients treated using standard outcome measures and send deidentified data from individual centers to the central registry. HBO2 treatment programs in the United States, United Kingdom, and Australia participate. Demographic, outcome, complication, and treatment data, including pre- and post-treatment quality of life questionnaires (EQ-5D-5L) are collected on individuals referred for HBO2 treatment. Out of 9726 patient entries, 378 individuals were treated for 45 emerging indications. Post-acute sequelae of COVID (PASC) (149/378 40%), ulcerative colitis (47/378 12.4%), and Crohn's disease (40/378 11%), accounted for 62% of total cases. Calciphylaxis (20/378 5.3%), frostbite (18/378 4.8%), and peripheral-vascular-disease related wounds (12/378 3.2%) accounted for a further 13.2%. PASC patients reported significant improvement on the Neurobehavioral Symptom Inventory (NSI pre 30.6, NSI post 14.4, p<0.001). Crohn's disease patients reported significantly improved quality of life (EQ-5D pre 53.8, post 68.8) and 5 reported closing a fistula. Ulcerative colitis patients showed strong trends toward improved quality of life and lower reported lower scores on a bowel questionnaire examining frequency, blood, pain, and urgency. A subset of calciphylaxis and arterial ulcer patients also reported improvement. HBO2 is being used for a wide range of possible applications across various medical specialties for its hypoxia-relieving and anti-inflammatory effects. Results show statistically significant improvements in patient-reported outcomes for inflammatory bowel disease and PASC. HBO2 is also being used for frostbite, pyoderma gangrenosum, pterygium, hypospadias repair, and facial filler procedures. Other indications show evidence for improvement and the case series for all indications is growing in the registry. Derr1-10.2196/18857. RR2-10.2196/18857.