Background: No study has yet assessed the effect of medial open-wedge high tibial osteotomy (MOWHTO) on the patellofemoral joint according to postoperative alignment. Purpose: To evaluate the effect of MOWHTO on the patellofemoral joint according to postoperative alignment by comparing the cartilage status before and after surgery and assessing the clinical and radiological outcomes. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 135 patients who underwent MOWHTO were retrospectively investigated. The patients were divided into 3 groups according to the postoperative weightbearing line ratio (WBLR): undercorrection (WBLR <58.3%, lowest quartile), acceptable correction (WBLR of 58.3%-66.3%, middle 2 quartiles), and overcorrection (WBLR >66.3%, highest quartile). The postoperative change in the cartilage status was assessed arthroscopically during implant removal at 2 years after MOWHTO. The clinical and radiological outcomes were evaluated at a mean follow-up of 52.1 months. A regression analysis was performed to identify the factors affecting the deterioration of the patellofemoral joint cartilage status. A receiver operating characteristic curve was employed to identify the cutoff point for the postoperative WBLR associated with the deterioration of the cartilage status in the patellofemoral joint. Results: Of all patients, progression of cartilage degeneration was noted in 39.3% for femoral trochlea and 23.7% for patella. The incidence of cartilage progression was significantly higher in the overcorrection group than in the undercorrection and acceptable correction groups (femoral trochlea: undercorrection group = 30.3%, acceptable correction group = 32.4%, and overcorrection group = 61.8% [ P = .008]; patella: undercorrection group = 15.2%, acceptable correction group = 17.7%, and overcorrection group = 44.1% [ P = .005]). The functional outcomes, including Lysholm knee score, Knee injury and Osteoarthritis Outcome Score (Pain, Symptoms, and Activities of Daily Living subscales), and Shelbourne and Trumper score, were significantly worse in the overcorrection group. The regression analysis showed that only the postoperative WBLR had a significant effect on cartilage deterioration. The cutoff point for the postoperative WBLR associated with progression of the International Cartilage Repair Society grade was 62.1% for the femoral trochlea (sensitivity = 61.5%, specificity = 62.7%, accuracy = 66.2%) and 62.2% for the patella (sensitivity = 59.4%, specificity = 60.2%, accuracy = 67.8%). Conclusion: The patellofemoral joint was adversely affected by MOWHTO. Overcorrection causing excessive valgus alignment led to further progression of degenerative changes in the patellofemoral joint and inferior clinical outcomes. The postoperative WBLR can be used as a predictive factor for deterioration of the cartilage status in the patellofemoral joint after MOWHTO.