Purpose <p>This study had two primary aims: (1) to evaluate the clinical efficacy of fluoroscopically-guided subchondral autologous bone marrow aspirate concentrate (BMAC) injection for reducing pain and improving function in patients with knee osteoarthritis (OA)-associated bone marrow lesions (BMLs), we hypothesized significant improvements across validated outcome measures at 12 months; and (2) to assess early radiologic changes in BML severity using MRI, hypothesizing a significant reduction in MOAKS scores at 3 months. Secondary aims evaluated subgroup differences by age and body mass index (BMI), with age stratified as ≤ 50, 50–60, 60–70, and &gt; 70 years, and hypothesizing superior outcomes in younger patients and those with lower BMI.</p> Methods <p>Retrospective evaluation of consecutive patients aged ≥ 18 years, with symptomatic knee OA and MRI-confirmed femoral or tibial subchondral BMLs, who underwent treatment between September 2022 and March 2024, with 12-month follow-ups ending in March 2025. Inclusion required BMI 18–30&#xa0;kg/m², neutral/varus limb alignment without deformity, intact cruciate ligaments/menisci, and no intra-articular injections within 12 months. Exclusion criteria included infection, BMI &gt; 30&#xa0;kg/m², ligament/meniscal injuries, or prior cellular therapy. Autologous BMAC was harvested from the posterior superior iliac crest, concentrated via density gradient centrifugation, and injected subchondrally under C-arm fluoroscopy. Primary outcomes included the Knee Injury and Osteoarthritis Outcome Score (KOOS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the Visual Analog Scale (VAS) at baseline and at 1, 3, 6, and 12 months. The secondary outcome was the MRI Osteoarthritis Knee Score (MOAKS) at baseline and at 3 months. Repeated measures ANOVA/Friedman tests were used; <i>p</i> &lt; 0.05 was considered significant.</p> Results <p>62 patients (mean age 57.7 ± 12.9 years; 56.5% female; mean BMI 24.4 ± 3.7&#xa0;kg/m²; 12-month follow-up) demonstrated significant improvements across all KOOS subscales (<i>p</i> &lt; 0.001), WOMAC (<i>p</i> &lt; 0.001), and VAS (<i>p</i> &lt; 0.001) versus baseline. MOAKS scores reduced significantly at 3 months (<i>p</i> &lt; 0.001). Patients with BMI &lt; 24&#xa0;kg/m² showed superior KOOS-pain improvement at 12 months (<i>p</i> = 0.043) and within this group, MOAKS scores significantly improved at 3 months (<i>p</i> &lt; 0.001). Patients ≤ 60 years exhibited greater VAS reduction at 1 month (<i>p</i> = 0.021) than those &gt; 70 years.</p> Conclusion <p>In this retrospective case series, fluoroscopically guided subchondral BMAC injection was associated with significant and sustained clinical improvement in pain and function over 12 months, alongside an early reduction in MRI-detected bone marrow lesion severity at 3 months. Because MRI assessment was limited to the early postoperative period, no conclusions can be drawn regarding the durability of structural changes or lesion resolution. These findings are encouraging and warrant confirmation in randomized controlled trials incorporating longer-term and quantitative MRI follow-up.</p> Level of Evidence <p>IV</p>