Background: Time-dependent postoperative changes in knee joint line obliquity (KJLO) and subsequent adaptational changes in the hip and ankle joints have not been fully proven after medial open wedge high tibial osteotomy (MOWHTO). Purpose: To investigate the serial postoperative changes in KJLO and subsequent adaptational changes in the hip and ankle joints over time after MOWHTO. Study design: Case series, Level of evidence, 4. Methods: A total of 92 patients who underwent MOWHTO between April 2015 and December 2020 were evaluated. Radiographic parameters, including KJLO, ankle joint line obliquity (ALO), hip abduction angle (HAA), joint line convergence angle, weightbearing line ratio, and hip-knee-ankle angle, were analyzed in time sequence (preoperatively and 3, 6, 12, and 24 months postoperatively). Repeated-measures analysis of variance and post hoc analysis were used to demonstrate alterations and the statistical significance of KJLO and other related radiographic parameters over time. Results: The mean KJLO values were –1.9°, –2.1°, –2.7°, and –3.2° at 3, 6, 12, and 24 months postoperatively, respectively, indicating that there was consistent increase in valgus tilting of KJLO from 6 to 24 months ( P < .001 for both 6-12 months and 12-24 months). ALO and HAA showed significant changes from 6 to 12 months (ALO, P < .001; HAA, P = .002), but not between 12 and 24 months (ALO: –3.0°, –2.7°, –1.9°, and −1.6°; HAA: –0.8°, –0.9°, –1.5°, and −1.8° at 3, 6, 12, and 24 months, respectively). The mean joint line convergence angle, weightbearing line ratio, and hip-knee-ankle angle did not change significantly from 3 months to 24 months postoperatively. Conclusion: There was a consistent increase in valgus tilting of the postoperative KJLO from 6 to 24 months after MOWHTO. The adaptive ALO and HAA significantly changed between 6 and 12 months and were maintained until 24 months after MOWHTO. It is necessary to consider the adaptive change when hip or ankle surgery is planned within this period.