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Background: Major complications of diabetes mellitus include lower leg and foot ulcers, which can result in amputation. Further study is needed to determine optimal treatments for these challenging wounds. Growth factor therapy and hyperbaric oxygen (HBO) treatments are 2 advanced therapeutic modalities that hold promise., Purpose: This descriptive, retrospective review investigated healing rates of patients with diabetes mellitus and lower- extremity ulcers managed by growth factor therapy and HBO as compared to standard wound care., Design: Retrospective review of medical records., Subjects and Setting: We reviewed medical records of 89 patients with diabetes and lower-extremity wounds treated at a major outpatient wound care program in the southwestern United States., Methods: Patients were categorized according to 4 treatment modalities: (1) standard wound care, (2) growth factor therapy, (3) standard wound care plus HBO, and (4) growth factor therapy plus HBO. Wounds were measured at the start of the analysis and then weekly for a total of 8 weeks. The change in wound volume from the first to the eighth week was recorded., Results: All patient groups demonstrated healing with the patients who received growth factor therapy alone and those who received growth factor therapy and the HBO treatments demonstrating the greatest decrease in wound volume over the 8 weeks. A 2-by-2 factorial analysis of covariance demonstrated that patients who received HBO as part of their wound care regimen demonstrated significantly greater healing than patients who received only standard wound care or growth factor therapy (P < .0001). Although the combination of hyperbaric and growth factor therapy did not show significant synergistic effects for wound healing in this study, it should be noted that the mean size of the wounds in this group was 2.8 times larger than the mean size of the wounds in the other groups., Conclusion: Patients managed in a state-of-the-art wound care center experienced progress toward wound healing, regardless of the treatment modality selected. Those who received HBO as part of their wound care regimen healed faster than those who received standard treatment or growth factor therapy.