[Abstract] Objective To compare the safety and clinical efficacy of simultaneous bilateral total knee replacement with that of unilateral total knee replacement. Methods We retrospectively counted 117 patients with knee osteoarthritis who were admitted to our orthopedic joint group from April 2010 to June 2012 and followed up for 1 year, and divided into a bilateral knee replacement group (26 patients) and a unilateral knee replacement group (91 patients) according to whether simultaneous bilateral knee replacement was performed, and compared the preoperative factors, intraoperative factors, postoperative conditions, hematological indexes, preoperative and 1-year postoperative HSS scores, length of hospital stay, and costs. The preoperative factors included age, gender, height, weight, body mass index, disease duration and preoperative comorbidities; intraoperative factors included operative time, intraoperative tourniquet time, intraoperative bleeding volume; postoperative condition included postoperative wound drainage, blood transfusion volume, proportion of patients with plasma or albumin transfusion and complications; hematological indexes included preoperative and postoperative hemoglobin volume, plasma albumin volume and total protein volume. The statistical analysis was done with SPSS18.0 software, and when P<0.05 was statistically significant. Results There was no statistically significant difference in the preoperative factors between the two groups of cases (P>0.05); there was no significant difference in the intraoperative factors of tourniquet time per side and operation time in the bilateral knee replacement group compared with the single knee replacement group (P>0.05), but there was more intraoperative bleeding in the bilateral knee replacement group than in the single knee replacement group (P<0.05); in the postoperative situation, there was no statistically significant difference in the incidence of complications between the two groups of cases (P> 0.05), but the proportion of patients with postoperative wound drainage, blood transfusion, and plasma or albumin transfusion were more in the double-knee replacement group than in the single-knee replacement group (P<0.05); there was no statistical difference in the preoperative hematological indexes between the two groups of cases (P>0.05), but the amount of hemoglobin, plasma albumin, and total protein were lower in the double-knee replacement group than in the single-knee replacement group after surgery (P<0.01); the two groups The preoperative HSS scores of the two groups were similar (P>0.05), and there was no statistical difference in HSS recovery between the two groups 1 year after surgery (P>0.05); the length of hospital stay in the bilateral knee replacement group was shorter than that in the unilateral knee replacement group by a factor of 2, and the cost (after deducting the cost of the prosthesis) in the bilateral knee replacement group was less than that in the unilateral knee replacement group by a factor of 2. All these differences were statistically significant (P<0.05). Conclusion Based on adequate preoperative preparation and skilled surgical technique, simultaneous bilateral knee replacement has comparable safety and clinical efficacy to unilateral knee replacement.