128 patients with knee cartilage defect were randomized to compare the efficacy and safety of matrix-induced autologous chondrocyte implantation (MACI implant) and microfracture (MFX) surgery. Primary outcomes were mean improvement Knee Injury and Osteoarthritis Outcome Scores (KOOS) Pain and Function subscales, and secondary outcomes were mean improvement in KOOS ADL, knee-related QoL, and other symptoms subscales, response rate (>10-pt improvement in KOOS Pain and Function score), Modified Cincinnati Knee Rating System, IKDC Subjective Knee Evaluation Overall Score, and failure rate (surgical re-treatment due to treatment response failure). After 3 years, improvement in KOOS Pain and Function subscales was significantly greater in the MACI group compared to the MFX group, although difference in response rate between groups did not reach statistical significance. The MACI group also demonstrated significantly greater improvement in KOOS ADL, QoL, and Symptoms subscales, Cincinnati and IKDC scores after 3 years compared to the MFX group. Failure was documented in 1 patient in the MACI group and 3 patients in the MFX group.