【Abstract】Objectives This study aimed to evaluate the combined e?ect of antibiotic-loaded bone cement and vacuum sealing drainage (VSD) on soft tissue infection. Methods This prospective study enrolled 12 cases with soft tissue infection in our hospital between May 2018 and January 2019. Their wound infection causes were: posttraumatic lower limb infection in 7 cases, diabetic foot in 3 cases and infection after internal fixation in 2 cases. The bacterial cultures of the wound secretion showed that there were 7 cases of staphylococcus aureus, 3 cases of staphylococcus epidermidis, 1 case of pseudomonas aeruginosa, and 1 case of negative result. At the first stage，infection was eliminated by radical debridement and placement of antibiotic-loaded bone cement into the wound，while at the second stage，skin grafting or random skin flaps was performed on the soft tissue defect in 12 cases. Results Except for one pseudomonas aeruginosa infection wound, biomembrane could be seen on the wound surface after the first stage of operation in other 11 cases, and biomembrane cultures were negative. The histological characteristics of these membranes showed the formation of endothelial cells and macrophages. The skin grafting（9 cases）and random skin flaps（2 cases）seem well survived at the second stage, a case of pseudomonas aeruginosa infection wound healed with skin grafting after radical debridement for 3 times. The mean follow-up was 6 months (range,3–9 months). No infection reoccurred during the follow-up. Conclusions The antibiotic-loaded bone cement combined with VSD can control and cure the soft tissue infection, and the biomembrane induced by bone cement has the capability to creat great conditions for subsequent repair of skin grafting or random pattern skin flap.