Background: Soccer is a highly demanding sport for the knee joint, and chondral injuries can cause disabling symptoms that may jeopardize an athlete’s career. Articular cartilage lesions are difficult to treat, and the increased mechanical stress produced by this sport makes their management even more complex. Hypothesis: To evaluate whether the regenerative cell-based approach allows these highly demanding athletes a better functional recovery compared with the bone marrow stimulation approach. Study Design: Cohort study; Level of evidence, 2. Methods: Forty-one professional or semiprofessional male soccer players were treated from 2000 to 2006 and evaluated prospectively at 2 years and at a final 7.5-year mean follow-up (minimum, 4 years). Twenty-one patients were treated with arthroscopic second-generation autologous chondrocyte implantation (Hyalograft C) and 20 with the microfracture technique. The clinical outcome of all patients was analyzed using the cartilage standard International Cartilage Repair Society (ICRS) evaluation package. The sport activity level was evaluated with the Tegner score, and the recovery time was also recorded. Results: A significant improvement in all clinical scores from preoperative to final follow-up was found in both groups. The percentage of patients who returned to competition was similar: 80% in the microfracture group and 86% in the Hyalograft C group. Patients treated with microfracture needed a median of 8 months before playing their first official soccer game, whereas the Hyalograft C group required a median time of 12.5 months (P = .009). The International Knee Documentation Committee (IKDC) subjective score showed similar results at 2 years’ follow-up but significantly better results in the Hyalograft C group at the final evaluation (P = .005). In fact, in the microfracture group, results decreased over time (from 86.8 ± 9.7 to 79.0 ± 11.6, P < .0005), whereas the Hyalograft C group presented a more durable outcome with stable results (90.5 ± 12.8 at 2 years and 91.0 ± 13.9 at the final follow-up). Conclusion: Despite similar success in returning to competitive sport, microfracture allows a faster recovery but present a clinical deterioration over time, whereas arthroscopic second-generation autologous chondrocyte implantation delays the return of high-level male soccer players to competition but can offer more durable clinical results.