Cartilage defects occur in approximately 12% of the population and can result in significant function impairment and reduction in quality of life. Evidence for the variety of surgical treatments available is inconclusive. This study aimed to compare the clinical outcomes of patients with symptomatic cartilage defects treated with matrix-induced autologous chondrocyte implantation (MACI or microfracture (MF). Included patients were >or= 18 and <or= 50 years of age with symptomatic, post-traumatic, single, isolated chondral defects (4-10 cm2) and were randomised to receive MACI or MF. Patients were followed up 8-12, 22-26 and 50-54 weeks post-operatively for efficacy and safety evaluation. Outcome measures were the Tegner, Lysholm and ICRS scores. Sixty patients were included in a randomised study (40 MACI, 20 MF). The difference between baseline and 24 months post-operatively for both treatment groups was significant for the Lysholm, Tegner, patient ICRS and surgeon ICRS scores (all P < 0.0001). However, MACI was significantly more effective over time (24 months versus baseline) than MF according to the Lysholm (P = 0.005), Tegner (P = 0.04), ICRS patient (P = 0.03) and ICRS surgeon (P = 0.02) scores. There were no safety issues related to MACI or MF during the study. MACI is superior to MF in the treatment of articular defects over 2 years. MACI and MF are complementary procedures, depending on the size of the defect and symptom recurrence. The MACI technique represents a significant advance over both first and second generation chondrocyte-based cartilage repair techniques for surgeons, patients, health care institutions and payers in terms of reproducibility, safety, intraoperative time, surgical simplicity and reduced invasiveness.