Objective: To compare the clinical efficacy of vacuum-assisted closure (VAC) therapy and traditional wetto-dry dressing in the management of moderate to severe open soft tissue trauma of the lower extremity. Methods: A prospective randomized controlled trial was conducted on 196 patients with Gustilo-Anderson grade II–III open soft tissue injuries of the lower extremity admitted to a Level 1 trauma center between March 2021 and April 2024. Patients were randomly assigned to the VAC group (n=98) and the traditional dressing group (n=98). The VAC group received negative pressure wound therapy (NPWT) at -125 mmHg continuous suction, while the traditional group received daily wet-to-dry dressing changes with normal saline-soaked gauze. Primary outcome measures included wound healing time, complete wound closure rate at 8 weeks, and incidence of surgical site infection (SSI). Secondary outcomes covered frequency of dressing changes, patient-reported pain score (Visual Analogue Scale, VAS), length of hospital stay, and rate of skin graft or flap surgery. Results: The VAC group exhibited significantly shorter mean wound healing time (28.5 ± 6.2 days vs. 42.3 ± 8.7 days, P<0.001) and higher 8-week complete closure rate (89.8% vs. 65.3%, P<0.001) compared with the traditional dressing group. The incidence of SSI was significantly lower in the VAC group (8.2% vs. 24.5%, P<0.001). Patients in the VAC group reported lower mean VAS pain scores (3.1 ± 1.2 vs. 5.8 ± 1.5, P<0.001) and required fewer dressing changes per week (1.2 ± 0.3 vs. 7.0 ± 0.5, P<0.001). The rate of skin graft or flap surgery was 12.2% in the VAC group, significantly lower than 30.6% in the traditional group (P<0.01). Multivariate logistic regression analysis confirmed that VAC therapy was an independent protective factor for delayed wound healing (OR=0.21, 95% CI=0.10–0.44, P<0.001) and SSI (OR=0.28, 95% CI=0.12–0.65, P<0.01). Conclusion: Vacuum- assisted closure therapy significantly improves wound healing outcomes, reduces infection risk, alleviates patient pain, and decreases the need for reconstructive surgery in patients with open soft tissue trauma of the lower extremity, making it a superior alternative to traditional wet-to-dry dressing.