Background: This is an analysis of the prospective Study of the Treatment of Articular Repair (STAR) to evaluate the effectiveness of autologous chondrocyte implantation (ACI) in a subset of adult patients with osteochondritis dissecans (OCD) knee lesions. Hypothesis: Autologous chondrocyte implantation can improve clinical outcomes in patients with at least 1 chronic OCD lesion of the knee who failed a previous non-ACI cartilage repair treatment. Study Design: Case series; Level of evidence, 4. Methods: Forty patients with at least one failed non-ACI treatment for an OCD knee lesion received ACI in a multicenter study. The modified Cincinnati Knee Rating System, the Knee injury and Osteoarthritis Outcome Score (KOOS), and the Short-Form 36 Health Survey (SF-36) were used to assess patient outcomes at baseline and periodically to 48 months. Treatment failures, serious adverse events, and subsequent surgical procedures were recorded. Results: Thirty-two (80%) patients completed the 48-month study. Autologous chondrocyte implantation treatment was successful in 85% of patients. Mean (+/- standard deviation) overall knee condition score (modified Cincinnati) was 3.1 +/- 1.1 at baseline and 6.8 +/- 2.0 at month 48. Clinically and statistically significant (P < .001) mean improvements from baseline to month 48 for the KOOS were as follows: 51.5 to 79.5 (pain), 54.8 to 77.9 (symptoms), 27.5 to 63.6 (sports and recreation ability), 63.5 to 86.7 (activities of daily living), and 21.9 to 59.6 (knee-related quality of life). The mean improvement (P < .001) in overall health assessed by the SF-36 was 35.4 to 45.5. Thirty-five percent (n = 14/40) of patients had a subsequent surgical procedure, most frequently debridement of the cartilage lesion. Treatment failure occurred in 6 of 32 (19%) patients. Conclusion: Patients with OCD of the knee had statistically significant pain reduction and functional improvement for up to 48 months after ACI, despite the complexity and severity of the osteochondral lesions.