Objective: To analyze the clinical effect of negative pressure drainage (VSD) combined with recombinant human acidic fibroblast growth factor (rh-aFGF) on refractory wounds and its influence on wound healing indexes of patients. Methods: 180 patients with refractory wounds treated in our hospital from July 2023 to July 2025 were randomly divided into observation group, control group A and control group B, with 60 patients in each group. The control group A was treated with routine dressing change, the control group B was treated with VSD, and the observation group was treated with VSD combined with rh-aFGF. The wound healing time, wound healing rate and total effective rate of the three groups were compared. The growth of granulation tissue on the wound surface; Microenvironment index of wound surface; Adverse reaction rate. Results: The wound healing time in observation group was shorter than that in control group A and control group B (P < 0.05). The wound healing rate of observation group was higher than that of control group A and control group B (P < 0.05). The total effective rate of observation group was higher than that of control group A and control group B (P < 0.05). After treatment, the granulation tissue coverage and granulation tissue thickness in the observation group were higher than those in the control group A and the control group B, while the wound pH value and the levels of IL-6 and TNF-α in exudate were lower than those in the control group A and the control group B (P < 0.05). The incidence of adverse reactions among the three groups was compared (P > 0.05). Conclusion: VSD combined with rh-aFGF can shorten the wound healing time, obtain good wound healing rate and total effective rate, promote granulation tissue growth, correct wound microenvironment disorder, and have good safety. Keywords: negative pressure drainage; Recombinant human acidic fibroblast growth factor; Refractory wound; Wound healing; Granulation tissue; Inflammatory factor