Background: Although medial open-wedge high tibial osteotomy (MOWHTO) is the treatment of choice for patients with mild to moderate osteoarthritis with varus malalignment, concerns about inferior outcomes in patients with preoperative radiological kissing lesion (RKL) remain. Purpose: To compare the mid- to long-term clinical and radiological results and survivorship after MOWHTO in patients with versus without preoperative RKL. Study Design: Cohort study; Level of evidence, 3. Methods: Included were 122 knees in patients who underwent MOWHTO with a medial locked plate and had minimum 5-year follow-up data. The mean age at surgery was 55.9 years (range, 38-65 years), and the mean follow-up was 7.5 years (range, 5-12.8 years). All patients had undergone second-look arthroscopy around 2 years after MOWHTO. The knees were divided into an RKL group (n = 17) and no-RKL group (n = 105) based on preoperative standing radiographs. The authors compared postoperative American Knee Society (AKS) knee and function scores, range of motion, and improvements in AKS scores between groups, as well as hip-knee-ankle angle, medial proximal tibial angle, and joint-line convergence angle from preoperatively to postoperatively. Also compared were the degree of cartilage regeneration between first- and second-look arthroscopy and the survival rate after index surgery. Results: Preoperative AKS scores were significantly lower in the RKL group versus the no-RKL group (AKS knee, 79.6 ± 7.5 vs 83.8 ± 3.9, P = .037; AKS function, 68.8 ± 9.3 vs 76.0 ± 5.1, P = .006). Likewise, postoperative AKS scores were significantly lower in the RKL group versus the no-RKL group (AKS knee: 91.3 ± 4.2 vs 94.4 ± 1.6, respectively, P = .008; AKS function: 90.0 ± 10.0 vs 97.6 ± 4.5, respectively, P = .007). However, all patients had excellent postoperative AKS knee and function scores (>80). Moreover, there were no between-group differences in pre- to postoperative improvement in AKS scores, postoperative radiological changes, or grade of cartilage regeneration. The survival rates in the RKL and no-RKL groups were 100% and 97.1%, respectively ( P ≥ .999). Conclusion: Although the latest clinical scores were lower in the RKL group than in the no-RKL group, comparable results in postoperative clinical improvement, cartilage regeneration, and survivorship were observed in patients with RKL at mid- to long-term follow-up.