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Peterson’s pioneering experience with the first clinical application of autologous chondrocyte implantation showed improvement in clinical outcomes, durable as much as 11 years, for a difficult patient population. An assessment of the general applicability of this technology in the United States requires long-term, multicenter followup. The purpose of this multicenter cohort study was to assess the clinical outcomes of patients treated with autologous chondrocyte implantation for lesions of the distal femur. Modified 10-point scales of the Cincinnati knee rating system were used to measure outcomes assessments at baseline and at 5 years. Eighty-seven percent (87 of 100) of patients completed 5-year followup assessments. Patients were an average 37 years of age, had a mean total defect size of 4.9 cm2, and had low baseline overall condition scores. At least one prior cartilage repair procedure had failed in 70% of the patients. At followup, 87 patients reported a mean improvement of 2.6 points in the overall condition score, including 62 with improved conditions, six with no change in condition, and 19 with worsened conditions. Of the 62 patients who improved, the mean overall condition score improved 4.1 points at followup. Patients treated with autologous chondrocyte implantation for large cartilage defects in the distal femur reported improvement in outcome scores at 5 years followup.Level of Evidence: Therapeutic study, Level II-1 (prospective cohort study). See the Guidelines for Authors for a complete description of levels of evidence.