Purpose Autologous Matrix-Induced Chondrogenesis (AMIC(A (R))) utilizing a type I/III collagen membrane was compared with microfracture (MFx) alone in focal cartilage lesions of the knee at one, two and five years. Methods Forty-seven patients (aged 37 +/- 10 years, mean defect size 3.6 +/- 1.6 cm(2)) were randomized and treated either with MFx, with sutured or glued AMIC(A (R)) in a prospective multicentre clinical trial. Results After improvement for the first two years in all subgroups, a progressive and significant score degradation was observed in the MFx group, while all functional parameters remained stable for least five years in the AMIC(A (R)) groups. At two and five years, MRI defect filling was more complete in the AMIC(A (R)) groups. No treatment-related adverse events were reported. Conclusions AMIC(A (R)) is an effective cartilage repair procedure in the knee resulting in stable clinical results significantly better than the MFx group at five years.