Abstract: Objective To investigate the effectiveness of vancomycin powder (VP) in the local joint in primary total knee arthroplasties (TKA), and provide a theoretical basis for clinical treatment. Methods A total of 290 patients diagnosed as end-stage knee osteoarthritis who underwent primary unilateral TKA between June 2014 and June 2018 were randomly divided into VP group (n=178) and control group (n=112) based on whether use high-dose VP before the capsule suture. In the VP group, 1 g of vancomycin was used in the powder state without solution. There were no significant difference in sex, age, body mass index, hemoglobin content, serum albumin and preoperative complications between the two groups (P>0.05). The operation time, hemoglobin and albumin levels, aseptic exudation of incision, subcutaneous hematoma, delayed healing, skin necrosis, prosthetic joint infection (PJI), deep venous thrombosis of lower limbs, pulmonary embolism and acute renal injury were recorded. Results There was no statistical difference in PJI rates between VP group (2.81%) and control group (2.68%) , χ²=0.066, P=0.947. There was no statistical difference in aseptic exudation of incision between VP group (6.18%) and control group (3.57%) , χ²=0.977, P=0.329. The rate of prolonged operative wound healing in VP group (8.99%) was higher than that in control group (2.68%) , χ²=2.114, P=0.035). There was no significant difference in the incidence of superficial skin infection, skin necrosis, deep vein thrombosis and pulmonary embolism between the two groups (all P>0.05). Conclusion Local application of VP in primary TKA cannot reduce the incidence of PJI, but increase the incidence of aseptic complications of incision, so it is not recommended to use vancomycin in the primary TKA.