Hyalograft C is an innovative tissue-engineering approach for the treatment of knee cartilage defects involving the implantation of laboratory expanded autologous chondrocytes grown on a three-dimensional hyaluronan-based scaffold. This technique has recently been introduced into clinical practice, with more than 600 patients treated so far. Because no periosteal coverage is required to keep the graft in place, surgical time and morbidity are reduced, and handling of the graft is much simpler than currently available autologous chondrocyte implantation techniques. The safety profile of the treatment appears positive, with a limited number of adverse events reported. Here we discuss the clinical, arthroscopic and histological results from a cohort of 67 patients treated with Hyalograft C (mean follow-up time from implantation of 17.5 months). Results are reported based on four endpoints: patients' subjective evaluation of knee conditions (97% of patients improved) and quality of life (94% improved), surgeons' knee functional test (87% of patients with the best scores), arthroscopic evaluation of cartilage repair (96.7% biologically acceptable) and histological assessment of the grafted site (majority of specimens hyaline-like). The positive clinical results obtained indicate that Hyalograft C may be a viable therapeutic option for the treatment of acute cartilage lesions.