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The optimal treatment for cartilage lesions has not yet been established. The objective of this randomized trial was to compare autologous chondrocyte implantation with microfracture. This paper represents an update, with presentation of the clinical results at five years.Eighty patients who had a single chronic symptomatic cartilage defect on the femoral condyle in a stable knee without general osteoarthritis were included in the study. Forty patients were treated with autologous chondrocyte implantation, and forty were treated with microfracture. We used the International Cartilage Repair Society, Lysholm, Short Form-36, and Tegner forms to collect clinical data, and radiographs were evaluated with use of the Kellgren and Lawrence grading system.At two and five years, both groups had significant clinical improvement compared with the preoperative status. At the five-year follow-up interval, there were nine failures (23%) in both groups compared with two failures of the autologous chondrocyte implantation and one failure of the microfracture treatment at two years. Younger patients did better in both groups. We did not find a correlation between histological quality and clinical outcome. However, none of the patients with the best-quality cartilage (predominantly hyaline) at the two-year mark had a later failure. One-third of the patients in both groups had radiographic evidence of early osteoarthritis at five years.Both methods provided satisfactory results in 77% of the patients at five years. There was no significant difference in the clinical and radiographic results between the two treatment groups and no correlation between the histological findings and the clinical outcome. One-third of the patients had early radiographic signs of osteoarthritis five years after the surgery. Further long-term follow-up is needed to determine if one method is better than the other and to study the progression of osteoarthritis.Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.