Objective To analyze the effect of vacuum sealing drainage (VSD) combined with recombinant human acidic ffbroblast growth factor (rh-aFGF) on wound healing-related indicators in patients with refractory wounds. Methods A total of 180 patients with refractory wounds treated in our hospital from July 2023 to July 2025 were selected, and they were divided into control group A, control group B and the observation group by the random number table method, with 60 patients in each group. Control group A received routine dressing change, control group B received VSD treatment, and the observation group received VSD combined with rh-aFGF treatment. The wound healing-related indicators, granulation tissue growth, wound microenvironment indicators and adverse reaction rate were compared among the three groups. Results The wound healing time of the observation group was shorter than that of control group A and control group B, and the difference was statistically signiffcant (P<0.05). The wound healing rate of the observation group was higher than that of control group A and control group B after 2 and 4 weeks of treatment, and the difference was statistically signiffcant (P<0.05). After treatment, the granulation tissue coverage rate and granulation tissue thickness in the observation group were higher than those in control group A and control group B, while the wound pH value, IL-6 and TNF-α levels were lower than those in control group A and control group B, the differences were statistically signiffcant (P<0.05). There was no signiffcant difference in the incidence of adverse reactions among the three groups (P>0.05). Conclusion VSD combined with rh-aFGF in the treatment of patients with refractory wounds can shorten wound healing time, achieve a good wound healing rate, promote granulation tissue growth, and correct wound microenvironment disturbance, without increasing the incidence of adverse reactions.