The aim of this study was to determine if a negative pressure wound therapy (NPWT) system can facilitate wound healing and withstand mechanical stress owing to the high range of motion of the knee joint in total knee arthroplasty. The benefits of NPWT include aiding wound granulation and a reduction in wound edema and secretion; our goal is to investigate its benefits in primary wound closure. Within an eight-day duration of treatment, we compared standard wound dressing (gauze and compression) with the disposable NPWT system (PICO)^TM. A total of 79 patients were recruited in a controlled, randomized, prospective, single-institution clinical trial. A total of 40 patients were allocated to the study group and 39 to the control group. In terms of blood loss and infection parameters, there was no significant difference between both groups. In the NPWT group, we determined a significant reduction in wound edema but none in wound secretion. While the NPWT dressings survived the mechanical effects of movement during postoperative physiotherapy, conventional compressive dressings were often renewed. Even though the risk factors that could lead to delayed wound healing were reduced in the test group, we could not identify any significant difference pertaining to delayed wound healing that required surgical treatment.