The aims of the study were to evaluate long-term outcomes after autologous matrix-induced chondrogenesis (AMIC) in the treatment of focal chondral lesions and to assess the possible improvements given by the combination of this technique with bone marrow aspirate concentrate (BMAC). Twenty-four patients (age range 18-55 years) affected by focal knee chondral lesions were treated with standard AMIC or AMIC enhanced by BMAC (AMIC+). Pain (Visual Analogue Scale (VAS)) and functional scores (Lysholm, International Knee Documentation Committee (IKDC), Tegner, Knee injury and Osteoarthritis Outcome Score (KOOS)) were collected pre-operatively and then at 6, 12, 24, 60, and 100 months after treatment. Magnetic resonance imaging (MRI) evaluation was performed pre-operatively and at 6, 12, and 24 months follow-ups. Patients treated with AMIC+ showed higher Lysholm scores (p = 0.015) and lower VAS (p = 0.011) in comparison with patients in the standard AMIC group at the 12 months follow-up. Both treatments allowed for functional and pain improvements with respect to pre-operative levels lasting up to 100 months. MRI revealed consistent cartilage repair at 24 months in both groups. This study shows that AMIC and AMIC+ are effective treatments for focal chondral lesions with beneficial effect lasting up to 9 years. AMIC+ allows for faster recovery from injury, and is thus more indicated for patients requiring a prompt return to activity. Level of evidence: II, randomized controlled trial in an explorative cohort.