BACKGROUND: In recent years, tranexamic acid has been extensively used to mitigate the substantial blood loss associated with total knee arthroplasty. However, the optimal method of topical application has not yet been established. OBJECTIVE: To evaluate the effectiveness and safety of intraoperative topical application of tranexamic acid combined with physical compression dressing in reducing perioperative blood loss in total knee arthroplasty. METHODS: A retrospective analysis was conducted on 90 patients who underwent total knee arthroplasty at the Honghui Hospital in Xi’an from January 2021 to December 2022. Based on the different topical use methods of tranexamic acid during surgery, patients were divided into three groups, with 30 cases in each group. In the compression dressing group, 2 g of tranexamic acid was placed in the articular cavity, and after packing the wound with gauze and cotton pads, a bandage was used to compress the wound. In the periarticular injection group, 2 g of tranexamic acid was injected into the surrounding tissue of the articular cavity. In the intra-articular injection group, 2 g of tranexamic acid was injected into the articular cavity. The blood loss, operation time, coagulation indicators, inflammatory indicators, and postoperative complications of the three groups were statistically analyzed. RESULTS AND CONCLUSION: (1) In terms of total blood loss, hidden blood loss, and maximum hemoglobin drop, the periarticular injection group had the least amount, and there was no statistically significant difference between the compression dressing group and periarticular injection group (P > 0.05). In terms of intraoperative blood loss, the compression dressing group had the least amount, and there were statistically significant differences compared with the periarticular injection group and intra-articular injection group (P < 0.05). There was no statistically significant difference in operation time among the three groups (P > 0.05). (2) There were no statistically significant differences in coagulation indicators (D-dimer and fibrinogen degradation products) and inflammation indicators (C-reactive protein and erythrocyte sedimentation rate) among the three groups preoperatively and on the first and third days after operation (P > 0.05). (3) There was no statistically significant difference observed among the three groups in terms of slow blood flow in the affected limb, intramuscular venous thrombosis, soft tissue swelling, and incidence of wound complications (P > 0.05). Additionally, no cases of deep vein thrombosis or pulmonary embolism were detected in any of the groups. (4) The topical application of tranexamic acid combined with compression dressing achieves the same effect as a periarticular injection in terms of simplicity of operation and reduced perioperative blood loss. This method also avoids the trauma caused by repeated punctures and does not increase the incidence of postoperative complications, making it a worthwhile option for clinical promotion. [ABSTRACT FROM AUTHOR]