Abstract: [Objective] To evaluate the clinical efficacy of antibiotic-loaded bone cement combined with vacuum-assisted closure for tibiofibular fracture of Gustilo type Ⅲ. [Methods] A retrospective study was performed on 60 patients who received surgical treatment of tibiofibular fracture of Gustilo type Ⅲ in our hospital from March 2020 to September 2021. According to the consequence of preoperative doctor-patient communication, 31 patients were treated with Antibiotic-loaded bone cement combined with VAC (the united group), while the remaining 29 patients were treated with single VAC (the VAC group). The documents regarding to perioperative period, laboratory tests and follow-up were compared between the two groups. [Results] All patients in both groups had the two-stage operations performed successfully without serious complications. There were no significant differences in the primary operation time and VAS scores between the two groups (P>0.05). The time before surgery, exudation rating, granulation rating, bacterial culture negative conversion rate, wound closure mode, wound healing time, hospital stay and treatment cost of the united group were significantly better than those of the VAC group (P<0.05).With respect of laboratory tests, the WBC, NEU, CRP, and ESR decreased significantly over time in both groups (P<0.05), which in the united group were significantly better than those in VAC group before the second stage operation (P<0.05). Fracture healing time and fracture healing in the united group were significantly better than those in the VAC group (P<0.05). Local scarring and limb function improved significantly over time in both groups (P<0.05). The local scarring and limb function in the united group were significantly better than those in the VAC group at 3 months after surgery (P<0.05), there were no significant differences in local scarring and function of affected limb between the two groups at 6 and 12 months after surgery (P>0.05). Patient satisfaction in the united group was significantly higher than that in the VAC group (P<0.05). [Conclusion] Compared with VAC treatment alone, Antibiotic-loaded bone cement combined with vacuum-assisted closure has the advantages of shortening the treatment period, reducing the risk of infection and promoting fracture healing.