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Autologous chondrocyte implantation (ACI) has not been proven to be durable over the long-term. The purpose of this systematic review was (1) to evaluate activity level and knee function, (2) to evaluate reoperation and failure rates, and (3) to analyze risk factors for reoperation and failure of ACI at minimum long-term follow-up.A comprehensive review was performed for studies with long-term outcomes after ACI for cartilage defect repair. Studies reported outcome scores such as Tegner score, Lysholm score, and International Knee Documentation Society (IKDC) score along with rates of failure and reoperation. Modified Coleman Methodology Scores were calculated to assess study methodological quality.Nine studies with a total of 771 patients with a mean age of 33.4 ± 2.5 years, mean defect size of 5.9 ± 1.6 cm2, and mean follow-up of 11.4 years were included. Tegner score, Lysholm score, and IKDC score change from preoperative to final follow-up was 1.1 (95% CI 0.8-1.4, P < 0.001), 24.9 points (95% CI 18.8-31, P < 0.001), and 16.5 points (95% CI 5.4-27.5, P < 0.01), respectively. The mean failure and reoperation rates were 18% and 37%, respectively. Increased age and lesion size (>4.5 cm2) were significantly correlated with increased risk of reoperation and failure.Overall, ACI demonstrated successful outcomes in 82% of patients over the long-term. Increased patient age and lesion size greater than 4.5 cm2 were risk factors for a higher reoperation and failure rate. Nonetheless, this review is limited by heterogeneity in surgical technique, and lesion and patient characteristics.