Diabetic foot ulcer management presents a significant challenge for wound care clinicians; numerous approaches to encourage healing in these difficult wounds have been explored. To determine risk factors related to diabetic foot ulcer time to healing and closure, a secondary analysis of data from a prospective randomized study involving 245 patients treated with a bioengineered human dermal substitute (n = 130) or control treatment (n = 115) was conducted. Analyzed variables included age, race, gender, ulcer duration, initial ulcer size, initial hemoglobin (HgbA1c), average HgbA1c, change in HgbA1c, diabetes type, average hours of weight-bearing, study ulcer infection, history of smoking or alcohol use, and laboratory values. Time to healing was significantly affected by initial ulcer size (risk ratio 0.75, confidence interval 0.59-0.96), gender (risk ratio 2.01, confidence interval 1.20-3.40), and wound infection during the study (risk ratio 2.9, confidence interval 1.45-4.22). Initial ulcer size (>2 cm2), male gender, and an episode of infection during the study were associated with an increased risk of nonclosure after 12 weeks of care (P <0.05). In patients whose HgbA1C increased during the study (n = 101), 20.7% of all wounds and 21% of dermal substitute-managed wounds (n = 105) healed; whereas, in patients whose HgbA1C levels remained stable or decreased, 26.3% of all wounds and 47% of dermal substitute-managed wounds healed (P <0.05). Female gender, small ulcer size, and the absence of infection were found to have a positive effect on healing all diabetic foot ulcers; improved glucose control had a significant effect on healing wounds managed with the dermal substitute only. This is the first diabetic foot ulcer study to find a relationship between hyperglycemia and wound healing. Further research into factors that improve healing of wounds, including diabetic foot ulcers, is warranted.