Abstract:[Objective] To compare the clinical efficacy of 3D printed patient-specific instruments (PSI) versus conventional instru-ments (CI) in total knee arthroplasty (TKA). [Methods] A retrospective study was conducted on 100 patients who received primary unilater-al TKA from January 2019 to December 2021. According to preoperative doctor-patient communication, 47 patients had TKA performedwith PIS, while the other 53 patients were treated with CI. The perioperative, follow-up and imaging data of the two groups were compared.[Results] Although the PSI group consumed significantly longer operation time [(80.0±12.7) min vs (66.1±12.3) min, P<0.05], and signifi-cantly higher hospital expense [(5.0±1.0) ten thousand yuan vs (4.2±0.5) ten thousand yuan, P<0.05] than the CI group, the former provedsignificantly superior to the latter in terms of incision length [(9.2±1.5) cm vs (14.0±2.6) cm, P<0.05], intraoperative blood loss [(42.0±10.8)ml vs (50.1±12.8) ml, P<0.05], postoperative drainage [(124.5±23.6) ml vs (154.3±20.7) ml, P<0.05], postoperative walking time [(24.0±4.5)hours vs (28.3±5.6) hours, P<0.05] and hospital stay [(6.8±2.6) days vs (9.0±3.0) days, P<0.05]. The follow-up period lasted for (18.0±3.5)months on a mean, and the PSI group resumed full weight-bearing activities significantly earlier than the CI group [(20.6±2.8) days vs(25.0±3.0) days, P<0.05]. The HSS score and knee extension-flexion ROM significantly increased, whereas the VAS and WOMAC scoressignificantly decreased in both groups over time (P<0.05), which proved not statistically significant between the two groups at any timepoints accordingly (P>0.05). Radiographically, the PSI group also proved significantly superior to the CI group in terms of FTA deviation[(1.0±0.3)° vs (2.2±0.7)°, P<0.05], FFC deviation [(0.4±0.1)° vs (1.3±0.5)°, P<0.05], FTC deviation [(0.2±0.0)° vs (1.2±0.3)°, P<0.05], LFCdeviation [(4.0±0.9)° vs (8.8±1.3)°, P<0.05] and LTC deviation [(0.5±0.1)° vs (0.9±0.3)°, P<0.05]. [Conclusion] The TKA with 3D-printedpatient-specific instruments achieve similar consequence to conventional instruments. Although this personalized technique consumes rela-tively longer operation time, it has obvious advantages over the conventional technique in restoring the coronal alignment of lower extremity and reducing intraoperative blood loss.