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Osteochondritis dissecans (OCD) is a disorder of unknown origin that can affect knees in skeletally mature and immature patients. Surgical management is an important cornerstone of treatment for unstable OCD lesions.To determine the (1) healing rate after internal fixation of unstable OCD between skeletally immature and mature knees, (2) risk factors for failure, and (3) patient-reported outcomes among healed patients.Cohort study; Level of evidence, 3.A multicenter retrospective cohort study was conducted with patients who underwent internal fixation of unstable knee OCD lesions from 2000 to 2015. Skeletal immaturity was defined as open or partially open physes. Healing was assessed through clinical findings and imaging. Definitive reoperation for the same OCD lesion was classified as failure.Among 87 patients included, 66 (76%) had healed lesions at ≥2 years postoperatively, while 21 (24%) failed. Skeletal maturity made no significant difference in failure rate (risk ratio, 0.68; 95% CI, 0.29-1.72; P = .40). For skeletally immature patients, lateral versus medial condylar location conferred an increased hazard of 18.2 (95% CI, 1.76-188.07; P < .01). Multivariate analysis factoring in skeletal maturity showed that lateral condylar location was an independent risk factor for failure (hazard ratio, 4.25; 95% CI, 1.47-19.85; P < .01). Mean patient-reported outcome scores (International Knee Documentation Committee [IKDC] and Knee injury and Osteoarthritis Outcome Score [KOOS]) increased significantly after surgery, except the KOOS symptoms score for the skeletally mature group. Final scores (mean ± SD) were as follows at a mean follow-up of 60 months (range, 24-166): IKDC, 83.5 ± 20.2; KOOS pain, 89.7 ± 14.1; KOOS symptoms, 87.4 ± 18.4; KOOS activities of daily living, 93.9 ± 12.7; KOOS sports, 80.7 ± 25.9; KOOS quality of life, 78.9 ± 23.1.Skeletally immature and mature patients heal at comparable rates after internal fixation of OCD lesions, resulting in functional and subjective improvement. Lateral femoral condylar lesion location is an independent risk factor for failure.