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Background: There is debate regarding the influence of a surgeon’s experience with computer-assisted surgery (CAS) on the postoperative mechanical axis (MA) in CAS-high tibial osteotomy. The purpose of the present study was to compare radiographic results between early and late cohorts of a consecutive series of patients to assess the influence of CAS experience on accuracy and precision of the postoperative MA during CAS lateral closingwedge high tibial osteotomy (LCWHTO). Materials and methods: Results from 140 CAS-LCWHTO operations were retrospectively reviewed. The first 70 cases, performed during the learning curve period for CAS between 2005 and 2009, were considered to be the “early cohort.” The subsequent 70 cases, performed with greater CAS experience after the completion of the learning curve between 2009 and 2014, were considered to be the “late cohort.” The target postoperative MA angle was valgus 3°. Pre- and postoperative MA angles were evaluated by navigation and radiographs. The proportion of postoperative MA inliers (≤ target angle ±3°) was investigated radiographically. The correlation between the navigation and radiographic measurements was analyzed. Results: The average postosteotomy MA angle on navigation was 3.4° in both cohorts. The average postoperative MA angle on radiographs was 1.0° in the early cohort and 2.2° in the late cohort (P = 0.003). Radiographically, the proportion of postoperative MA inliers was greater in the late cohort than in the early cohort (early versus late, 71.4% versus 90%; P = 0.011). The pre- and postoperative correlation between navigation and radiographic measurements was also stronger in the late cohort (early versus late; preoperative r = 0.558 versus 0.663; postoperative r = 0.310 versus 0.376). Conclusions: Greater experience with CAS increased the accuracy and precision of postoperative MA alignment as well as the correlation between navigation and radiographic measurements. Caution should be taken during registration procedures to achieve accurate alignment correction in CAS-LCWHTO.