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Objective: To determine and compare failure, re-operation, and complication rates of all generations and techniques of autologous chondrocyte implantation (ACI).Methods: A systematic review of multiple medical databases was performed according to PRISMA guidelines. Levels I-IV evidence were included. Generations of ACI and complications after ACI were explicitly defined. All subject and defect demographic data were analyzed. Modified Coleman Methodology Scores (MCMSs) were calculated for all studies.Results: 82 studies were identified for inclusion (5276 subjects were analyzed; 6080 defects). Ninety percent of the studies in this review were rated poor according to the MCMS. There were 305 failures overall (5.8% subjects; mean time to failure 22 months). Failure rate was highest with periosteal ACI (PACI). Failure rates after PACI, collagen-membrane cover ACI (CACI), second generation, and all-arthroscopic, second-generation ACI were 7.7%, 1.5%, 3.3%, and 0.83%, respectively. The failure rate of arthrotomy-based ACI was 6.1% vs 0.83% for all-arthroscopic ACI. Overall rate of re-operation was 33%. Re-operation rate after PACI, CACI, and second-generation ACI was 36%, 40%, and 18%, respectively. However, upon exclusion of planned second-look arthroscopy, re-operation rate was highest after PACI. Unplanned re-operation rates after PACI, CACI, second-generation, and all-arthroscopic second-generation ACI were 27%, 5%, 5%, and 1.4%, respectively. Low numbers of patients undergoing third-generation ACI precluded comparative analysis of this group.Conclusions: Failure rate after all ACI generations is low (1.5-7.7%). Failure rate is highest with PACI, and lower with CACI and second-generation techniques. One out of three ACI patients underwent a re-operation. Unplanned re-operations are seen most often following PACI. Hypertrophy and delamination is most commonly seen after PACI. Arthrofibrosis is most commonly seen after arthrotomy-based ACI. Use of a collagen-membrane cover, second-generation techniques, and all-arthroscopic, second-generation approaches have reduced the failure, complication, and re-operation rate after ACI. [ABSTRACT FROM AUTHOR]