Problem: Articular cartilage lesions are founded in more than 60% of knee arthroscopies. Regenerative techniques for cartilage repair based on cultured autologous chondrocytes offer hyaline-like cartilage repair, in comparison with bone marrow stimulation techniques that lead to fibrous tissue formation with inferior quality and less durability. Purpose: To evaluate the clinical and sequential imaging follow-up results at a mean of sixty-months after all arthroscopic Matrix Encapsulated Autologous Chondrocyte Implantation (MECI) versus Microfracture (MFx) techniques for the treatment of articular cartilage lesions in the knee. Material and Methods: Fifty consecutive patients with symptomatic articular cartilage lesions in the knee, 1-4cm2 size, grade III-IV (ICRS) were randomized into two groups: MECI or MFx. In MECI group twenty-six patients were included and two osteochondral biopsies were harvested in the first surgery. Isolated chondrocytes were expanded in monolayer culture during four weeks. A construct was formed with a collagen type-III scaffold enveloped in chondrocytes monolayers. In the second surgery, debridement of the lesion was performed and construct was fixed with a bio absorbable mini-anchor for condylar lesions or with a suture-passing technique for patellar lesions with an all-arthroscopic novel technique. In MFx group 24 patients were treated with arthroscopic microfractures as traditionally described by Steadman. The patients were evaluated clinically using International Knee Documentation Committee (IKDC), Lysholm, and Tegner scores. T2-Mapping-MRI was also performed evaluating six regions of interest (ROI): ROI-3 represents mean value of healthy native cartilage while ROI-6 is the mean of repaired tissue evaluation. Results: The demographics and comorbid conditions known to affect outcome of chondral repair techniques were similar between the groups (mean age was 35.05 years). At five years follow up there was no significant statistical difference in the clinical evaluation with the scores Lysholm (78 ± 24.37, 77.25 ± 22.74: p=0.168), Tegner (5 ± 2.55, 4.18 ± 1.97: p=0.095), IKDC (72.97 ± 18.10, 65.17 ± 22.74: p=0.438) between MECI and Microfracture, respectively. However, T2-mapping evaluation showed significant difference between MECI and MFx, respectively (38.05 ± 6.25, 45.41 ± 10.49; p=0.040) favoring MECI group. Conclusion: Patients with MECI and Microfracture technique obtained better clinical results than preoperatively with no significant differences between groups at five-years follow-up. However, MECI group patients had better tissue quality measured by T2-Mapping MRI.