In a 2024 multicenter registry of 9,726 hyperbaric oxygen treatment entries, 378 patients (3.9 percent) were treated for 45 conditions that fall outside FDA-cleared indications. Post-COVID condition, ulcerative colitis, and Crohn’s disease were the three most common off-label uses, together making up 62 percent of those cases. Off-label HBOT is legal and widespread, but the evidence behind it ranges from randomized trials to anecdote.
Part of the BaricBoost HBOT Data series. Cite as: “Off-Label HBOT: How Many Conditions Are Treated Outside FDA Clearance? (2026 Data),” BaricBoost.com, 2026.
How common is off-label HBOT use?
“Off-label” means using an FDA-cleared device for a condition not on the cleared list. It is legal and common across medicine. In the 2024 International Multicenter Registry for Hyperbaric Oxygen Therapy (Tanaka et al.), 378 of 9,726 patient entries (3.9 percent) were treated for indications outside those approved by the Undersea and Hyperbaric Medical Society.1 That 378-patient group is the denominator for every off-label percentage below. The off-label share is far higher outside hospital wound-care centers, reaching most or all of the volume in freestanding clinics and home chambers.
Key terms
- Off-label use: treating a condition with an FDA-cleared device or drug for an indication the FDA has not cleared. Legal when based on clinical judgment and informed consent.
- FDA-cleared indication: a specific condition for which the FDA has authorized a device or therapy, backed by submitted evidence.
- Registry study: a study that prospectively collects real-world outcome data from many centers, useful for spotting emerging uses but not a substitute for randomized trials.
Which conditions are treated with off-label HBOT?
From the International Multicenter Registry for Hyperbaric Oxygen Therapy (Tanaka et al., 2024), the most common off-label indications, as a share of the 378 off-label patients, were:1
Top off-label HBOT conditions (registry data, N=378)
| Condition | Patients | % of off-label cases | Key outcome |
|---|---|---|---|
| Post-COVID condition (Long COVID) | 149 | 39.4% | NSI score 30.6 to 14.4 (P<0.001) |
| Ulcerative colitis | 47 | 12.4% | Improved quality of life, lower bowel scores |
| Crohn’s disease | 40 | 10.6% | EQ-5D 53.8 to 68.8; 13% closed a fistula |
| Calciphylaxis | 20 | 5.3% | Subset reported improvement |
| Frostbite | 18 | 4.8% | Case-level improvements |
How strong is the evidence for each off-label use?
Off-label does not mean unproven, and it does not mean proven. The conditions span the full evidence spectrum, from randomized trials to FDA consumer warnings.
Off-label conditions by evidence level
| Evidence level | Conditions | Study type |
|---|---|---|
| Strong emerging (RCTs) | Long COVID, IBD (Crohn’s, ulcerative colitis) | Randomized controlled trials |
| Moderate (cohort / case studies) | TBI, calciphylaxis, frostbite, fertility | Phase I/II trials, prospective studies |
| Weak (anecdotal) | Anti-aging, athletic recovery, Lyme disease, autism | Case reports, anecdotes |
| No evidence / FDA-warned | Cancer, Alzheimer’s, Parkinson’s, ADHD | Not recommended |
The anti-aging claims illustrate the weak tier. They trace largely to a single small 2020 study by Hachmo and colleagues in Aging reporting increased telomere length in 35 older adults, which has not been replicated in outcome trials.5 That is a mechanistic signal, not proof of an anti-aging effect.
Why is Long COVID the leading off-label use?
Long COVID is the most common emerging indication in registry data, at 39.4 percent of off-label cases, and it has the strongest supporting trial evidence of the off-label group.1 In the registry cohort, Neurobehavioral Symptom Inventory scores improved from 30.6 to 14.4 (P<0.001). Separately, a randomized sham-controlled trial by Zilberman-Itskovich and colleagues (2022) in 73 post-COVID patients found significant improvements in cognitive function, energy, sleep, and brain perfusion on MRI.3 That combination of registry and RCT data is why Long COVID sits in the strongest off-label tier.
What about TBI and the $28 million trial?
Traumatic brain injury is one of the most active areas of off-label HBOT research. According to USF Health, a $28 million clinical trial at the University of South Florida is enrolling more than 400 veterans to evaluate HBOT for TBI and PTSD using a randomized design.6 The result will help settle a long-running debate, since earlier military trials produced mixed findings. Off-label use of HBOT for TBI today rests on cohort and case-series data, which is why it sits in the moderate tier rather than the strong one.
What does the FDA say about off-label HBOT?
The FDA has explicitly warned consumers that HBOT has not been proven to treat cancer, autism, diabetes, Alzheimer’s, or Parkinson’s disease, and cautions against clinics marketing it for those uses.2 Off-label use by a licensed practitioner is legal, but it should rest on clinical judgment and informed consent, not marketing. The FDA-cleared and Medicare-covered indications are a much shorter list, defined in Medicare National Coverage Determination 20.29.4 The documented success rates are strongest for those approved indications, and for genuine emergencies such as carbon monoxide poisoning.
Where is off-label HBOT most common?
Setting predicts the off-label share more than any single condition does:
- Hospital wound care centers: under 5 percent off-label (insurance-driven, limited to cleared indications)
- Freestanding HBOT clinics: roughly 30 to 50 percent off-label (a mix of cleared and cash-pay off-label)
- Integrative and functional medicine practices: largely off-label
- Home chambers: almost entirely off-label
Research interest continues to grow. As of 2026, ClinicalTrials.gov lists numerous active HBOT trials, with Long COVID, TBI and concussion, and cognitive decline among the most studied off-label targets.7 Exact counts shift with each query date, so treat any single figure as a snapshot.
Sources
- Tanaka HL, Rees JR, Zhang Z, et al. “Emerging Indications for Hyperbaric Oxygen Treatment: Registry Cohort Study.” Interactive Journal of Medical Research, 2024;13:e53821. doi:10.2196/53821. PMID: 39078624
- U.S. Food and Drug Administration. “Hyperbaric Oxygen Therapy: Get the Facts.” FDA Consumer Update. fda.gov
- Zilberman-Itskovich S, Catalogna M, Sasson E, et al. “Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: randomized controlled trial.” Scientific Reports, 2022;12:11252. doi:10.1038/s41598-022-15565-0
- Centers for Medicare & Medicaid Services. “National Coverage Determination (NCD) for Hyperbaric Oxygen Therapy (20.29).” CMS.gov
- Hachmo Y, Hadanny A, Abu Hamed R, et al. “Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells: a prospective trial.” Aging, 2020;12(22):22445-22456. doi:10.18632/aging.202188
- USF Health. “Veterans powering landmark hyperbaric oxygen research.” University of South Florida, 2025. usf.edu
- ClinicalTrials.gov. Active hyperbaric oxygen therapy trials (accessed 2026). clinicaltrials.gov
Medical Disclaimer
The content on BaricBoost.com is for informational purposes only and is not intended as a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
Author
Seph Fontane Pennock is the founder of BaricBoost.com and Regenerated.com, a clinic directory for regenerative medicine serving 10,000+ providers across the United States. He previously built and sold PositivePsychology.com, which grew to 19 million users and became the largest evidence-based positive psychology resource on the web. Seph brings direct experience as an HBOT patient, having completed protocols at clinics across three continents while navigating mold illness, systemic inflammation, and autoimmune conditions. His treatment journey includes hyperbaric oxygen therapy, peptide protocols, NAD+ therapy, and consultations with specialists from Dubai to Cape Town to Mexico. This combination of entrepreneurial track record and lived patient experience shapes everything published on BaricBoost.com. Every article is grounded in peer-reviewed research, informed by real clinical encounters, and written for patients making high-stakes treatment decisions. Seph's focus is on bringing transparency, scientific rigor, and practical guidance to the hyperbaric oxygen therapy space.
