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Aim: Morel-Lavallée lesion (MLL) is the separation of the skin from the deep fascia caused by shear stress after trauma and the formation of a fluid-filled cavity between the fascia layers. After the inflammation develops, a fibrous capsule develops around the serosanguineous fluid, preventing its absorption. Cavity infection, skin necrosis, and muscle, tendon, bone, and implant exposure were observed in untreated MLLs. This study presents vacuum-assisted surgical treatment for large and complex MLLs and the effects of treatment on the functionality of lower extremities. Methods: 23 patients who were diagnosed with post-traumatic MLL in the lower extremities and underwent vacuum-assisted surgical treatment were examined. Demographic characteristics, comorbidities, smoking status, body mass index (BMI), type of trauma, anatomical location, skin characteristics of the cavity, additional injuries, duration of treatment delay, medical and surgical procedures, return to work, and social life were investigated. All cavities were evaluated using ultrasonography, and cavity volumes were measured. All patients underwent percutaneous incision drainage and radical debridement of necrotic tissues and cavities. Lower extremity function was evaluated using the lower extremity functional scale (LEFS). Results: A total of 82.6% of patients had chronic MLLs. All patients had high-volume MLLs and functional impairment due to MMLs. The vacuum-assisted wound closure provided compression, drainage, and obliteration of the cavity alone in the treatment of MLL. Additionally, the positive effects of negativepressure wound therapy (NPWT) on wound healing prevented complications such as recurrent MLLs, seroma, dehiscence, and graft loss. This method has also positively affected lower-extremity functionality during subsequent periods (p<0.001). Conclusions: In treating large-volume acute and chronic MLLs, percutaneous drainage, radical debridement, cavity closure with quilting sutures, and pressure support with NPWT are reliable methods that ensure problem-free healing of MLLs. This method has also positively affected lower-extremity functionality during subsequent periods. [ABSTRACT FROM AUTHOR]