OBJECTIVES: About 10-15% of individuals with diabetes mellitus develop foot ulcers which precede 85% of amputations.  Increased oxygen exposure, through the use of hyperbaric oxygen therapy (HBOT), has been suggested to encourage ulcer healing thus reducing the risk of amputation.  The objective of this systematic review is to evaluate the efficacy of systemic HBOT for non-healing ulcers of the lower limb in diabetes patients. METHODS: A systematic search of the published literature was conducted using controlled and keyword terms focusing on “HBOT” and “lower limb diabetic ulcers”.  Databases searched included Medline, EMBASE, CINAHL, PubMed, Wiley’s Cochrane Library, and Biosis.  Randomized controlled trials (RCTs) and observational studies were included and no year or language limits were employed.  Two reviewers screened the articles.  Pooled estimates of outcomes were calculated using Review Manager when appropriate. RESULTS: Of the 543 citations identified, 152 articles underwent full-text review. Data was abstracted from 27 publications (7 RCTs, 9 comparative observational, and 11 non-comparative observational studies). Primary outcomes of rates of amputation (major or minor) and wound healing were identified.  Relative risk (RR) estimates from RCTs in the pooled analysis reflect a significant reduction in major amputation (RR = 0.32, 95% CI 0.11 to 0.91) with HBOT.  For the proportion of unhealed wounds, HBOT is also favoured (RR = 0.45, 95% CI 0.32 to 0.64). CONCLUSIONS: The limited RCT evidence surrounding the efficacy of HBOT favours the use of HBOT for non-healing wounds of the lower limb for diabetes patients.  Rigorous clinical trials with larger sample sizes, however, need to be conducted to more conclusively establish the benefits and harms of treating diabetic lower limb ulcers with HBOT.