Objective To study the clinical effect of expanded skin grafting combined with vacuum sealing drainage (VSD) in the treatment of patients with refractory wounds. Methods A total of 92 patients with refractory wounds admitted to Guizhou Provincial People's Hospital from January 2020 to December 2022 were selected as observation objects, and they were divided into control group and observation group according to random number table method, with 46 patients in each group. The control group was treated with expanded skin grafting, and the observation group was treated with expanded skin grafting combined with VSD. The clinical efficacy pain, inflammatory factor levels and complications were compared between the two groups. Results The total effective rate of the observation group was 93.48%, which was higher than 76.09% of the control group (P<0.05). The VSA scores of treatment in the first three dressing changes in the observation group were lower than those in the control group (P<0.05). the levels of CRP, IL-6 and PCT in the observation group were lower than those in the control group on 7 days after treatment (P<0.05). The incidence of complications in the observation group was 4.35%, which was lower than 28.26% in the control group (P<0.05). Conclusion For patients with refractory wounds, expanded skin grafting combined with VSD treatment is helpful to improve wound healing, and can effectively reduce the level of inflammatory factors, the incidence of complications and the degree of pain during dressing change, which can further improve the clinical efficacy