Objective: This study aimed to investigate the efficacy of intralesional epidermal growth factor (EGF) in preventing the extremity from a major amputation and its effects on wound healing in chronic diabetic foot ulcers (DFUs).Material and Methods: Thirty-three patients with DFUs were treated with intralesional EGF application between January 2013 and January 2017.The first endpoint was to determine the prevention rate of major amputation within 12 months following treatment. The second endpoints were therecovery of ulcer surface area with ≥ 50% granulation following two months and the healing of ulcer surface area with ≥ 75% granulation following sixmonths after the first application of EGF.Results: After three patients were excluded because of major side effects in the remaining 30 patients (48 DFUs), granulation rate of ≥ 50% was achievedin 24 (37 DFUs) patients, and not achieved in 6 (11 DFUs) patients eight weeks following the EGF application. A granulation rate of ≥ 75% was achieved in21 (31 DFUs) patients after six months. At 12 months following the treatment, one major and seven minor amputations were performed, a total of 10 DFUsin five patients were not healed, and the DFUs in 17 patients completely recovered.Conclusion: Intralesional EGF application has positive results in addition to good foot care in DFUs, and promising results can be obtained by protecting the extremity from amputation by using it in patients whose vascular intervention methods are not appropriate and have DFUs that do not healwith conventional wound care treatments.