The aim of this study was to compare the clinical outcome of cartilage repair with autologous chondrocyte implantation (ACI) in patients with osteochondritis dissecans (OCD) lesions and full-thickness cartilage lesions. This study included a cohort of 115 consecutive patients with a cartilage lesion of the knee treated with ACI. Of the patients, 35 had an OCD lesion and 80 a full-thickness cartilage lesion. During a follow-up period from 2 to 13 years all treatment failures were identified. The failure rate between OCD lesions and full-thickness cartilage lesions was compared with Kaplan-Meier analysis. Patient-reported outcome was evaluated 2 years postoperatively with the Lysholm score. During the follow-up 21 out of 115 patients encountered a treatment failure. The failure rate for full-thickness cartilage lesions was 19.1% and for OCD lesions 43.3% over the 10-year follow-up. Patient-reported outcome improved from baseline to 2 years postoperatively. The improvement from baseline was statistically significant, and the Lysholm score improved more than the minimal clinically important difference. The patient-reported outcome showed no difference between lesion types at 2 years. In the presented retrospective study, the failure rate of first-generation ACI was higher in OCD lesions than in large full-thickness cartilage lesions, suggesting that OCD lesions may associate with properties that affect the durability of repair tissue. Future prospective studies are needed to tell us how to best repair OCD lesions with biological tissue engineering.