This study aimed to describe the midterm clinical and radiographic outcomes of a hybrid fixation technique (HFT) combining interfragmentary compression with screws and biological support provided by the osteochondral autograft transplantation system (OATS) for treating large unstable juvenile osteochondritis dissecans (JOCD) lesions involving the knee in patients aged ≤18 years. Thirteen patients (15 knees, 9 males) with unstable JOCD lesions in the knee underwent treatment. HFT was indicated for lesions that had a completely salvageable (N=10) or partially salvageable progeny fragment (N=5). Patients were evaluated at a minimum follow-up of 1 year. The mean age of the patients was 15.3 years (range, 11 to 18y), with 10 lesions involving the medial femoral condyle and 5 involving the lateral femoral condyle. The mean lesion area were 397.7mm2. The outcome measures included the Pedi-IKDC and Tegner activity scales. Radiographic evaluation consisted of assessing osteochondral graft integration using the MOCART score on MRI and determining the degree of osteoarthritis using the Kellgren-Lawrence system (KL). At a mean follow-up of 51 months (range, 12 to 143mo), the mean Pedi-IKDC and Tegner activity scale were 90.1±7.2 and 94.7±6.7 points, respectively. Patients with unilateral lesions resumed sports activities on average after 7.7 months (range, 6 to 12mo). All patients exhibited progeny fragment integration on MRI, with a mean MOCART score of 85±6.5 (range, 75 to 95). Radiographs indicated grade 1 KL joint space in 13 knees and grade 2 in 2 knees. At the last follow-up, 12 patients were asymptomatic, whereas 1 patient experienced occasional mild discomfort during intense physical activity. Six patients required additional surgery for hardware removal, and 1 patient underwent intra-articular loose body removal. The hybrid fixation technique showed promising outcomes in terms of fragment healing and midterm results for unstable JOCD lesions. These findings suggest that HFT can be considered a valid treatment option for large unstable lesions involving the femoral condyles of the knee in adolescents. Therapeutic study (level of evidence IV).