Diabetic foot ulcers (DFUs) remain one of the most consequential complications of diabetes. They are slow to heal, prone to infection, and strongly linked to lower-extremity amputation and reduced survival—mortality after a DFU has been estimated at roughly 5% within the first year and as high as 40% at five years. Because conventional care alone does not heal every wound, clinicians have long looked to adjunctive treatments. Hyperbaric oxygen therapy (HBOT) is among the most studied—and most debated—of these. This article reviews how HBOT is thought to work, what the published evidence demonstrates, and where its limits lie.
How Hyperbaric Oxygen Therapy Is Thought to Work
HBOT involves breathing 100% oxygen inside a pressurized chamber, typically at 2 to 2.5 times atmospheric pressure, for sessions of roughly 90 minutes delivered five days per week over several weeks. The treatment dramatically raises the amount of oxygen dissolved in plasma, allowing oxygen to reach tissue beds that a compromised circulation cannot adequately supply.
Chronic diabetic wounds are frequently hypoxic. Poor perfusion, microvascular dysfunction, and high metabolic demand in infected tissue leave the wound bed starved of the oxygen needed for repair. By transiently flooding tissue with oxygen, HBOT is proposed to support several healing-related processes: stimulating new blood-vessel formation (angiogenesis), enhancing the bactericidal activity of white blood cells, promoting collagen synthesis and fibroblast function, and reducing edema. These mechanisms make HBOT biologically plausible as an adjunct—but plausibility is not the same as proven clinical benefit.
What the Evidence Shows on Wound Healing
The most influential synthesis remains the 2015 Cochrane systematic review by Kranke and colleagues, which pooled randomized controlled trials of HBOT for chronic wounds. Among people with diabetic foot ulcers, the review found a significant increase in the rate of ulcer healing at six weeks (risk ratio 2.35), but this short-term advantage was no longer evident at one-year follow-up. The authors emphasized that the contributing trials had important flaws in design and reporting, leaving the certainty of the findings low.
More recent meta-analyses have generally reported favorable healing outcomes while echoing the same caution about study quality. A 2022 systematic review and meta-analysis by Zhang and colleagues, pooling 20 randomized trials and over 1,200 patients, reported that HBOT increased the healing rate of DFUs and shortened healing time. A 2021 meta-analysis by Sharma and colleagues, drawing on 14 controlled studies, similarly found significantly higher complete-healing rates with HBOT compared with standard care. A 2024 network meta-analysis by OuYang and colleagues placed HBOT among several adjunctive therapies that outperformed standard care for complete ulcer healing.
Evidence on Amputation
Preventing amputation is arguably the outcome that matters most. Here the evidence is mixed but leans toward benefit in some analyses. The 2022 meta-analysis by Zhang and colleagues found a reduced incidence of major amputation with HBOT, and the 2021 analysis by Sharma and colleagues reported a significant reduction in major—though not minor—amputation. By contrast, the 2015 Cochrane review found no statistically significant difference in major amputation rates, with a wide confidence interval reflecting genuine uncertainty.
The discrepancy is instructive. Differences in patient selection (particularly the severity of underlying arterial disease), HBOT protocols, definitions of amputation, and trial quality all influence the results. This is why authoritative bodies continue to describe the amputation-prevention evidence as suggestive rather than definitive.
Interpreting the Controversy
Why does a therapy with a coherent biological rationale generate such inconsistent conclusions? Much of it comes down to methodology. Many trials are small, unblinded, and heterogeneous in how they enrolled patients and measured outcomes. A wound that is predominantly ischemic may respond differently than one that is primarily neuropathic, yet trials often mix these populations. Adjunctive benefit also depends on optimal background care: HBOT is not a substitute for debridement, offloading, infection control, glycemic management, and vascular assessment, and its value is best judged on top of those fundamentals rather than in place of them.
For these reasons, HBOT is generally positioned as a selective adjunct—considered for specific, carefully assessed wounds that are failing to progress despite comprehensive standard care—rather than as a routine treatment for all diabetic foot ulcers.
Clinical Takeaways
The balance of evidence indicates that hyperbaric oxygen therapy can improve short-term healing of diabetic foot ulcers and may reduce the risk of major amputation in selected patients, but the long-term healing advantage is uncertain and the quality of supporting trials is limited. HBOT works only as part of, not instead of, sound wound care. Patient selection appears critical, and larger, well-designed, adequately powered randomized trials are still needed to define exactly which patients benefit most. For clinicians and patients alike, the most accurate summary is one of cautious, evidence-tempered optimism.
References
- Kranke P, Bennett MH, Martyn-St James M, Schnabel A, Debus SE, Weibel S. Hyperbaric oxygen therapy for chronic wounds. Cochrane Database of Systematic Reviews. 2015;(6):CD004123.
- Zhang Z, Zhang W, Xu Y, Liu D. Efficacy of hyperbaric oxygen therapy for diabetic foot ulcers: an updated systematic review and meta-analysis. Asian Journal of Surgery. 2022;45(1):68–78.
- Sharma R, Sharma SK, Mudgal SK, Jelly P, Thakur K. Efficacy of hyperbaric oxygen therapy for diabetic foot ulcer, a systematic review and meta-analysis of controlled clinical trials. Scientific Reports. 2021;11(1):2189.
- OuYang H, Yang J, Wan H, Huang J, Yin Y. Effects of different treatment measures on the efficacy of diabetic foot ulcers: a network meta-analysis. Frontiers in Endocrinology. 2024;15:1452192.
- Everett E, Mathioudakis N. Update on management of diabetic foot ulcers. Annals of the New York Academy of Sciences. 2018;1411(1):153–165.
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