Objective?To analyze the effects and safety of different osteotomy sequences on knee joint function for patients undergoing total knee arthroplasty. Methods?The clinical data of 80 patients with intermediate and advanced knee arthritis who underwent total knee arthroplasty from January 2018 to December 2019 in Dongguan Chinese Medicine Hospital were retrospectively analyzed. According to the osteotomy sequence, the patients were divided into the group A (first tibial osteotomy, 40 cases) and the group B (first femoral osteotomy, 40 cases), both were followed up for 3 months after surgery. The perioperative indicators, changes in knee joint function before surgery, 1 and 3 months after surgery, and the occurrence of postoperative complications were compared between the two groups. Results?The operation time of the group B was significantly shorter than that of the group A, and the amount of intraoperative blood loss was significantly less than that of the group A, the anterior and posterior diameters of the medial and lateral tibial plateaus were significantly longer than those of the group A; compared with the preoperative period, the knee range of motion of the two groups of patients and the knee joint score of the American Hospital of Special Surgery (HSS) gradually increased in the 1st and 3rd months after the operation(all P<0.05); there was no significant difference in the incidence of knee joint range of motion, HSS score, postoperative wound infection, re-osteotomy, deep vein thrombosis, joint stiffness and knee pain between the two groups (all P >?0.05). Conclusion?First femoral osteotomy or tibial osteotomy in total knee arthroplasty can effectively improve the knee joint function in patients with advanced knee arthritis, but compared with tibial osteotomy first, femoral osteotomy can fully expose the tibia and optimize the operation during total knee arthroplasty shortens the operation time, reduces the scope of tibial osteotomy, reduces the amount of intraoperative blood loss, reduces the patient's postoperative knee pain, facilitate early postoperative activities for patients.