Abstract Objective Since the influencing factors of an excessively large mechanical medial proximal tibial angle (mMPTA) following open wedge high tibial osteotomy (OWHTO) remain unclear and there is a lack of domestic studies on this topic, a corresponding risk factor analysis was conducted. Methods A cross-sectional study was conducted using preoperative weight-bearing long-leg anteroposterior radiographs (LLRs) for OWHTO planning. Data were collected from Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine between December 2020 to October 2022. General patient data and lower limb alignment parameters were recorded, including the hip-knee-ankle angle (HKAA), weight-bearing line percentage (WBL pct.), mechanical lateral distalfemoral angle (mLDFA), joint line convergence angle (JLCA), and mMPTA. The classification of preoperative and postoperative coronal plane alignment of the knee (CPAK) based on the patient's lower limb alignment parameters. Based on postoperative mMPTA, patients were divided into two groups: mMPTA>95° and mMPTA≤95°. Multivariate logistic regression analyses were performed to identify factors influencing postoperative mMPTA. Results The study included 238 lower limbs from 168 patients. Preoperative CPAK classification was Type I (64.7%) and Type II (35.3%). Postoperative CPAK classification was primarily Type III (29.4%), Type VI (52.9%), and Type IX (16.4%). Postoperatively, 62 limbs had mMPTA>95°, and 176 had mMPTA≤95°. Univariate analysis showed significant differences (P<0.05) between groups in gender, age, preoperative mLDFA, preoperative HKAA, preoperative WBLpct., preoperative JLCA, and preoperative CPAK classification. Further multivariate logistic regression analysis indicated that larger preoperative mLDFA and JLCA ≥ 4° were independent risk factors for postoperative mMPTA > 95° (P<0.05), and both factors demonstrated high predictive value for postoperative mMPTA. Combining these two factors improved the predictive ability, with an area under the curve of 0.936 (0.905-0.968). Conclusion A larger preoperative mLDFA and JLCA are independent risk factors for excessive mMPTA after OWHTO in patients with unicompartmental knee osteoarthritis and varus deformity. Clinical emphasis should be placed on evaluating these risk factors to tailor the surgical approach.