Objective To investigate the application and effect of digitization threedimensional printing osteotomy guide in knee replacement.Methods We retrospectively analyzed the 80 patients with knee replacement received therapy from January 2015 to January 2019. According to the random number table, they were divided into observation group and control group. The observation group was treated with osteotomy with digitization threedimensional printing osteotomy guide. The control group was treated with osteotomy with conventional surgical instruments. The perioperative condition, imaging index, New York Special Surgery Hospital (HSS) scores, knee joint activity and adverse reactions were compared between the two groups.Results All the patients were successfully completed the operation. There were no serious complications in the perioperative period, and the incision was healed in the first stage. The tourniquet use time and operation time in the observation group were significantly shorter than that of the control group［(60.43±7.49) min vs (65.82±6.20) min, (102.49±8.74)min vs (118.43±9.01)min］. The intraoperative hemorrhage was less than that of the control group［(429.42±46.21)ml vs(531.21±57.64)ml］(P＜0.05). The whole lower limb force line and coronal force line of femoral prosthesisangle in the observation group were significantly smaller than that of the control group［(037±005)° vs (0.76±0.11)°, (90.11±1.30)°vs (90.97±1.65)°］(P＜0.05). The proportion of lower limb force line and femoral prosthesis outliers were significantly lower than that of the control group［7.50%vs25.00%, 5.00%vs20.00%］(P＜0.05). 3 months after operation, the HSS score and knee joint activity in the observation group were significantly higher than that of the control group［(83.22±5.75)scores vs (79.49±5.40)scores, (105.54±6.95)°vs(100.11±5.53)°］(P＜0.05). There was no hypersensitivity or immune rejection in the implant and host between two groups, and no infection or venous thrombosis. There was no loosening, dislocation or sinking of the prosthesis during the follow-up.Conclusion The digitization threedimensional printing osteotomy guide is well for knee replacement, which can effectively shorten the operation time, reduce the amount of bleeding during the operation, and more accurate correction of the lower limb force line, which is conducive to the recovery of knee joint activity.