Objective <p>Medial open-wedge high tibial osteotomy (MOWHTO) is an established joint-preserving procedure for medial compartment knee osteoarthritis associated with varus malalignment. However, while MOWHTO effectively corrects mechanical alignment, it does not directly address biochemical environment of the knee joint or concomitant full-thickness cartilage defects. Biological augmentation strategies such as microfracture (MFX) and bone marrow aspirate concentrate (BMAC) have been proposed to enhance cartilage regeneration and improve clinical outcomes. The purpose of this study was to compare clinical, radiological, and second-look arthroscopic outcomes of patients treated with MOWHTO combined with MFX, with or without BMAC augmentation.</p> Methods <p>A retrospective comparative study was conducted on 113 patients with medial compartment knee osteoarthritis who underwent MOWHTO and MFX between 2015 and 2022. All patients were followed-up for a minimum of 2 years. Patients were allocated into two groups: MOWHTO + MFX (Group I, <i>n</i> = 52) and MOWHTO + MFX + BMAC (Group II, <i>n</i> = 61). Clinical outcomes were evaluated using International Knee Documentation Committee (IKDC) and Lysholm scores. Cartilage regeneration was assessed during second-look arthroscopy at the time of plate removal using the International Cartilage Regeneration Society Cartilage Repair Assessment (ICRS-CRA) and Koshino staging systems. Radiological parameters including femorotibial angle and posterior tibial slope were also analyzed.</p> Results <p> Both groups demonstrated significant improvements in clinical and radiological outcomes at final follow-up. However, Group II showed significantly superior cartilage regeneration, with higher mean ICRS-CRA scores compared to Group I (9.50 ± 1.52 vs. 8.62 ± 1.51; <i>p</i> = 0.001), as well as ICRS-CRA grades and Koshino stages (<i>P</i> = 0.01 and 0.049, respectively). Clinical improvements were also greater in the BMAC group, with significantly higher postoperative IKDC and Lysholm scores and greater score improvements from baseline (all <i>p</i> &lt; 0.01). Radiological alignment correction was comparable between groups, with no loss of correction.</p> Conclusion <p>While MOWHTO combined with MFX provides effective mechanical realignment and clinical improvement, the addition of BMAC improves cartilage regeneration quality and leads to superior functional outcomes. However, the absolute differences in clinical scores remained below the reported minimal clinically important difference (MCID) thresholds in the literature, suggesting that the clinical relevance of these improvements may be limited. Therefore, while BMAC augmentation appears to enhance structural cartilage regeneration, its routine use should be carefully considered.</p> Level of evidence III <p>This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors <a href="http://www.springer.com/00266">www.springer.com/00266</a>.</p>