80 patients with an isolated knee cartilage lesion were randomized to undergo either autologous chondrocyte implantation (ACI) or microfracture (MFx). The purpose of this study was to compare clinical outcome measures and rate of failure (defined as a need for a secondary surgery due to symptom return) between groups over a 15-year follow-up. The rate of radiographic osteoarthritis development was also assessed. The results demonstrated no significant differences between groups in Lysholm, visual analog pain scale, Short Form 36-Item Physical Component score, and the incidence of failure after 15 years, the clinical scores of survivors (non-failures) in both groups demonstrated improvement from baseline values. Among survivors (non-failures), the incidence of radiographic osteoarthritis development was 48% and 57% in the ACI group and MFx group, respectively.