Osteochondral surgical procedures have been described for the treatment of unfixable osteochondritis dissecans (OCD), but only few of them have been studied for juvenile OCD (JOCD) lesions. A cell-free biomimetic osteochondral scaffold showed positive results in adult patients. The aim of this study was to evaluate the results of this scaffold for the treatment of knee JOCD at mid-term follow-up. Twenty patients (14 males, 6 females) were included in this study. Mean age was 16.2 ± 1.4 years, average defect size was 3.2 ± 1.8 cm2, and mean symptoms duration was 20.2 ± 17.9 months. After the implantation of the osteochondral collagen-hydroxyapatite scaffold (Maioregen, Fin-Ceramica, Faenza, Italy), patients were evaluated preoperatively and prospectively at 1, 2, and at final mean follow-up of 6 years (range 5-7 years) with International Knee Documentation Committee (IKDC) subjective and objective, Tegner, and EuroQol visual analogue scale (VAS) scores. MRI evaluation was performed with the MOCART 2.0 score. All scores showed a significant improvement. IKDC subjective score went from 50.3 ± 17.4 preoperative score to 75.3 ± 14.6 at 1 year (P = 0.002), 80.8 ± 14.6 at 2 years and 85.0 ± 9.3 at 6 years. The Tegner score improved from the preoperative evaluation of 2.6 ± 1.4 to 5.5 ± 2.0 at 6 years (P < 0.0005), although without reaching the level registered before the onset of symptoms. A longer symptoms duration influenced negatively IKDC subjective and Tegner scores up to 2 years (P = 0.003 and P = 0.002, respectively) but did not affect the final outcome. Lesion size did not affect the final result. The MOCART 2.0 score showed a significant improvement between 1-year and final follow-up, but with persisting subchondral alterations. This study demonstrated a clinical improvement stable over time with a high survival rate, although with persisting abnormal MRI findings, especially at subchondral bone level. This procedure can be considered a suitable option for the treatment of young patients affected by knee OCD. Level of evidence. Case series, level IV.