Objective To explore the effect of vacuum sealing drainage combined with free skin grafting and flap transplantation in the treatment of infected wounds and its influence on the degree of pain. Methods A total of 70 patients with infected wounds admitted to the Plastic and Reconstructive Surgery Department of Tianjin Hospital of ITCWM/Nankai Hospital from July 2020 to July 2023 were selected as the research objects. They were divided into control group and observation group by random number table method, with 35 patients in each group. The control group was treated with routine wound repair, and the observation group was treated with vacuum sealing drainage combined with free skin grafting and flap transplantation. The clinical related indexes, pain degree, wound healing and complications were compared between the two groups. Results The number of wound dressing changes in the observation group was less than that in the control group, and the use time of anti-infective drugs, wound healing time and total treatment time were shorter than those in the control group (P<0.05). The VAS score of the two groups before skin grafting/transplantation and on the day of suture removal was lower than that before treatment, and that of the observation group was lower than that of the control group (P<0.05). The excellent and good rate of wound healing in the observation group was 97.14%, which was higher than 80.00% in the control group (P<0.05). The incidence of complications in the observation group was 0, which was lower than 5.71% in the control group, and the difference was not statistically significant (P >0.05). Conclusion Vacuum sealing drainage combined with free skin grafting and flap transplantation is effective in the treatment of infected wounds, which can provide good conditions for the growth of new granulation, improve clinical related indicators, relieve pain, promote wound healing, without increasing the incidence of complications. It is worthy of clinical application.