Background: Different surgical approaches are currently available to treat knee chondral defects. Microfracture is the most commonly applied, but it often leads to a mechanically inferior fibrocartilaginous tissue. To overcome this shortcoming, the Autologous, Matrix-Induced Chondrogenesis (AMIC) technique has been proposed. To further enhance the outcome of AMIC, the addition of haemoderivatives containing growth factors that stimulate cartilage healing has emerged as a new treatment method. Recently, a novel leucocyte-platelet-concentrated membrane (CLP-MB), highly enriched in platelets, monocytes/macrophages, fibrinogen, CD34 + and CD34 + VEGFR-2 + CD133 + cells, has been developed. Additionally, an injectable collagen scaffold (Cartifill) has been proposed as a replacement of the AMIC standard collagen membrane., Aims: This preliminary study is aimed to evaluate the short-term safety and efficacy of the use of the CLP-MB membrane and injectable collagen scaffold when combined in single-step AMIC procedures for the treatment of knee chondral lesions., Methods: Medical records of patients who underwent an AMIC procedure with the CLP-MB membrane combined with Cartifill were reviewed retrospectively. Follow-up assessments were conducted at 6 and 12 months after surgery. Clinical function was assessed on the basis of the International Knee Documentation Committee (IKDC) score. Pain was evaluated using the visual analogue scale (VAS)., Results: Twenty-five patients were identified as meeting the inclusion criteria. Mean IKDC and VAS scores significantly improved during the follow-up time. The postoperative course was uneventful., Conclusions: AMIC combined with the CLP-MB membrane, and Cartifill seems to be a promising approach to treat knee chondral defects.