OBJECTIVE Conflicting evidence exists on the effects of hyperbaric oxygen therapy (HBOT) in the treatment of chronic ischemic leg ulcers. The aim of this trial was to investigate whether additionalHBOTwould benefit patientswith diabetes and ischemic leg ulcers. RESEARCH DESIGN AND METHODS Patients with diabetes with an ischemic wound (n = 120) were randomized to standard care (SC) without or with HBOT (SC+HBOT). Primary outcomes were limb salvage and wound healing after 12 months, as well as time to wound healing. Other end points were amputation-free survival (AFS) and mortality. RESULTS Both groups contained 60 patients. Limb salvage was achieved in 47 patients in the SC group vs. 53 patients in the SC+HBOT group (risk difference [RD] 10% [95% CI24 to23]). After 12months, 28 indexwoundswere healed in the SC group vs. 30 in the SC+HBOT group (RD 3% [95% CI 214 to 21]). AFS was achieved in 41 patients in the SC group and 49 patients in the SC+HBOT group (RD 13% [95% CI 22 to 28]). In the SC+HBOT group, 21 patients (35%) were unable to complete the HBOT protocol as planned. Thosewho did had significantly fewermajor amputations and higher AFS (RD for AFS 26% [95% CI 10-38]). CONCLUSIONS Additional HBOT did not significantly improve complete wound healing or limb salvage in patients with diabetes and lower-limb ischemia.