To analyze the clinical effect of vacuum sealing drainage (VSD) combined with skin grafting in the repair of ulcer wounds. Methods A total of 60 patients with chronic ulcer of lower limbs admitted to our hospital from October 2022 to October 2023 were randomly divided into control group and observation group, with 30 patients in each group. The control group was treated with VSD, and the observation group was treated with VSD combined with skin grafting. The clinical efficacy, clinical indicators, pain degree, bacterial negative conversion rate and scar condition were compared between the two groups. Results The total effective rate of treatment in the observation group was 96.67%, which was higher than 80.00% in the control group (P <0.05). The swelling and pain relief time, debridement time, healing time and hospitalization time in the observation group were shorter than those in the control group, and the skin graft survival rate was higher than that in the control group (P <0.05). After 2 and 4 weeks of treatment, the VAS score of the observation group was lower than that of the control group (P <0.05). The negative conversion rate of various bacteria in the observation group was higher than that in the control group (P <0.05). The VSS score of the observation group was lower than that of the control group (P <0.05). Conclusion VSD combined with skin grafting in the repair of ulcer wounds has a good effect, which can promote the rapid healing of ulcer wounds, improve the survival rate of skin grafting and the negative rate of bacteria. Meanwhile, it can effectively reduce pain and scar.