Objectives:High Tibial Osteotomy (HTO) is widely performed to treat early arthiritis in the varus knee. The aim of this prospective study is to evaluate different prognostic factors affecting the outcomes of HTO and, with special attention to the role of the site of deformity.Methods:231 Opening Wedge HTO (OWHTO) were performed in 202 patients and included in the study. Inclusion criteria were: 1) age > 18 years, 2) no major associated procedures (i.e. ACL reconstruction, major cartilage procedure, 3) only OWHTO, 4) pre-operative complete clinical and radiological evaluation available. Patients were evaluated with (1) the Knee Society score (KSS), (2) the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, (3) another self-evaluation scale, (4) long-leg radiographs, and (5) plain radiographs. On the x-ray different angles were evaluated, including Join Line Congruence Angle. Furthermore, the location of deformity was established. Three main outcomes were identified: Indication to Total Knee Arthroplasty (TKA), KSS poor or fair and WOMAC < 76 points), and different prognostic factors were identified (Fig. 1). All the variables were firstly tested in a single regression model to evaluate the association with each outcome. All the variables with p<0.1 were re-tested in a multiple regression model.Results:32 patients were lost to follow-up and 31 patients did not meet the inclusion criteria, leaving 139 patients (156 OWHTOs) for the study. The average age was 52.9 ± 9.6 years, and the average follow-up was 97.7 ± 42.8 months. Post-operatively there was a significant improvement in both the KSS and WOMAC score compared to the pre-operative period (p<0.0001). The only variable related to TKA indication was a pre-operative JLCA ≥5° (OR=24.3, p=0.0483). Conversely, different variables were related to a worse KSS, including pre-operative BMI >30 Kg/m2 (OR=78.9, p=0.0028), pre-operative ROM <120° of flexion (OR=40.8, p=0.0421), pre-operative mLDFA ≥91° (OR=36,6,p=0.0401) and femoral pre-operative CORA ≥3° of varus (OR=39,9 p=0.0269). Furthermore, a pre-operative BMI >30 Kg/m2 (OR=29,5, p=0.0314) was associated to a worse WOMAC score. Conversely, patients with a pre-operative mMPTA ≤84° had lower risk to obtain a worse KSS oe WOMAC score (respectively OR= 0,2 p=0.0364 and OR=0,3 p=0.0071). The cumulative survivorship was calculated with the Kaplan-Meier method, and it resulted equal to 98.6% at 5 years and decreased to 85.5% at 10 years.Conclusion:OWHTO is a good treatment for early arthritis in the varus knee if the correct indications are applied. The outcomes can be considered good, with 85% of 10-year survivorship. It is mandatory to correctly address the location of the deformity, because the presence of a femoral varus deformity is related to worse outcomes. Similarly, presence of a pre-operative JLCA ≥5° is the only factor associated to TKA indication.Table 1.Pre-OperativeIntra-OperativeBMIAssociated proceduresAge (≥56 years)Cartilage damageGender Educational status Post-Operative Amount of deformityWeight bearing line (%)ROMI (Range of motion)JLCAKnee Society scoremLDTA (mechanical lateral distal tibial angle)Function score WOMAC scale Amount of medial arthritis Presence of lateral arthritis mLDFA (mechanical lateral distal femoral angle) mMPTA (mechanical medial proximal tibial angle) JLCA (Joint Line Congruence Angle) Femoral CORA (center of rotation and angulation)