Background <p>Obesity contributes to the accelerated progression of knee osteoarthritis. Medial open-wedge high tibial osteotomy (MOWHTO) is a joint-preserving surgical intervention for unicompartmental knee osteoarthritis; however, its efficacy in patients with obesity remains controversial. This study aimed to evaluate the 5-year clinical and radiographic outcomes of MOWHTO with lateral supplemental lag screw fixation in patients with obesity.</p> Materials and methods <p>This retrospective cohort study included patients with obesity who underwent MOWHTO between 2017 and 2020, with a minimum follow-up of 5 years. All procedures were performed by a single surgeon using three-dimensional printed, patient-specific instrumentation, locking plates, and a lateral supplemental lag screw. Clinical outcomes were assessed using the visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Radiographic parameters, including the weight-bearing line percentage (WBL%) and medial proximal tibial angle (MPTA), were evaluated.</p> Results <p>Significant improvements in VAS and WOMAC scores were observed at all postoperative time points (<i>p</i> &lt; 0.001) and were accompanied by improved radiographic alignment, with WBL% shifting toward the Fujisawa point and increased MPTA values. At 5 years, mild regression in alignment was noted; however, the overall correction was maintained. The 5-year conversion rate of TKA was 3.8%. Lateral hinge fractures occurred in 3.8% of cases and healed without loss of correction.</p> Conclusions <p>Medial open-wedge high tibial osteotomy is associated with satisfactory 5-year clinical and radiographic outcomes in patients with obesity. Obesity is not necessarily a contraindication for HTO, although appropriate patient selection and long-term follow-up are essential for this procedure.</p> <p><i>Level of evidence</i>: III, Retrospective cohort study.</p>