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Background Wound healing complications are causal factors of prosthesis infection and poor postoperative evolution of patients after total knee arthroplasty (TKA). Negative-pressure wound therapy (NPWT) can be an option to minimize these complications. The aim of this study is to compare the complications of patients undergoing TKA who used a portable NPWT device in the immediate postoperative period with those of a control group. Methods A total of 296 patients were evaluated. Patients were divided into two groups: those who used NPWT for seven days in the postoperative period (Group 1 – prospective evaluated) and those who used conventional dressings (Group 2 – historical control group). Epidemiological data, comorbidities, local parameters related to the surgical wound and complications were evaluated. Results The groups did not differ in regard to sex, age and clinical comorbidities. Overall, 153 (51.7%) patients had at least one risk factor for wound complications. Patients who used NPWT had a lower rate of complications (28.5% vs. 45.7%, p = 0.001) and a lower rate of reintervention in the operating room (2% vs. 8.5%, p = 0.001). Patients in group 1 had a lower incidence of hyperaemia (14.7% vs. 40.2%, p = 0.01), skin necrosis (2.1% vs. 8.5%, p = 0.04) and wound dehiscence (3.1% vs 10.1%, p = 0.03). The use of NPWT was a protective factor for the presence of complications, with an odds ratio of 0.36 (95% CI 0.206–0.629). Conclusion The number of complications related to the wound after TKA is high; however, most of them are minor and have no impact on the treatment and clinical evolution of patients. The use of NPWT decreased the number of surgical wound complications, especially hyperaemia, dehiscence and necrosis, and reduced the need for reintervention.