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<b>Objective:</b> To explore the clinical effects of antibiotic bone cement and vacuum sealing drainage (VSD) combined with free chimeric anterolateral thigh perforator myocutaneous flaps for sequential treatment of diabetic calcaneal osteomyelitis wounds. <b>Methods:</b> This study was a retrospective investigation of case series. From June 2019 to June 2024, 12 patients with diabetic calcaneal osteomyelitis wounds who met the inclusion criteria were admitted to the Department of Burns and Plastic Surgery of Xiangya Hospital of Central South University, including 7 males and 5 females, aged 40 to 65 years. Of the 12 patients, 8 cases had Wagner grade Ⅲ wounds and 4 cases had Wagner grade Ⅳ wounds. Debridement+temporary antibiotic bone cement filling and coverage+VSD treatment was performed in stage Ⅰ, in which the wound area after debridement was 6 cm×5 cm to 18 cm×8 cm, and the bone defect volume was 1.0 cm×0.8 cm×0.5 cm to 1.8 cm×1.5 cm×0.8 cm. Free chimeric anterolateral thigh perforator myocutaneous flaps were used to repair the wounds in stage Ⅱ, in which the area of the perforator flap was 10.0 cm×5.0 cm to 20.0 cm×10.0 cm, and the area of the muscle flap was 3.0 cm×2.5 cm to 7.0 cm×6.0 cm. The wound in the flap donor area was directly sutured or repaired by split-thickness skin graft from the thigh. The white blood cell count, neutrophil, high-sensitivity C-reactive protein level, and microbial culture of wound secretion specimens at admission and 7 days after stage Ⅰ treatment, and the growth of wound-bed granulation tissue 7 days after stage Ⅰ treatment were recorded. After stage Ⅱ surgery, the flap survival and the wound healing in the donor and recipient areas were observed. During follow-up, the blood supply, appearance, and texture of the flap, whether ulcers and osteomyelitis recurred, the recovery of the donor areas, and the function of the affected limbs were observed. <b>Results:</b> Seven days after stage Ⅰ treatment, the white blood cell count, neutrophil, and high-sensitivity C-reactive protein level of patients were 7.15 (6.73, 8.70)×10<sup>9</sup>/L, 0.65 (0.63, 0.72), and 15.50 (12.48, 25.50) mg/L, respectively, which were significantly lower than 12.30 (11.28, 13.48)×10<sup>9</sup>/L, 0.80 (0.78, 0.83), and 73.20 (57.25, 93.75) mg/L at admission (with <i>Z</i> values of -2.905, -2.825, and -3.059, respectively, <i>P</i> values all <0.05). At admission, the microbial culture results of wound secretion specimens were all positive, and the redness and swelling around the wound were obvious. Seven days after stage Ⅰ treatment, the microbial culture results of wound secretion specimens were all negative, there was no obvious redness or swelling around the wound, and the wound-bed granulation tissue grew well. After stage Ⅱ surgery, only two patients had a small area of ischemic epidermal necrosis at the distal end of the flap, and the wounds healed with delayed healing after dressing changes; the flaps of the other patients all survived well and the wounds in the recipient areas all healed smoothly; the donor area wounds of all patients healed well. Follow-up for 6 to 18 months showed that the blood supply and appearance of the flaps were good, and the texture was soft; no recurrence of ulcers was observed, and no obvious signs of recurrence of osteomyelitis were shown by X-ray examination; the donor areas recovered well without obvious scar hyperplasia, and the affected limbs were all able to perform weight-bearing activities. <b>Conclusions:</b> Sequential treatment of diabetic calcaneal osteomyelitis wounds with antibiotic bone cement and VSD combined with free chimeric anterolateral thigh perforator myocutaneous flaps enables thorough removal of the infected lesions, and in addition, effective closure of deep dead space and soft tissue coverage of the calcaneus can be achieved. The short-term follow-up effect is good, and it is worthy of clinical promotion.