Different techniques have been proposed for the treatment of cartilage defects. Among the currently available options, autologous single-plug osteochondral transplantation is one of the few to be applied to address small and medium lesions. The goal of the current study was to document the long-term clinical outcome of a cohort of patients treated by this surgical strategy, which consists of harvesting a single osteochondral plug from a less weight bearing area of the knee and implanting it on the defect site by press-fit technique. Fifteen patients were enrolled. Age at surgery was 30.2±15.3 years, and body mass index was 22.5±3.0 kg/m(2). The inclusion criteria were clinical symptoms, such as knee pain or swelling, and grade III to IV chondral and osteochondral knee lesions. Patients were prospectively evaluated up to a mean of 17.5±3.5 years of follow-up by using Lysholm, International Knee Documentation Committee (IKDC) subjective, and Tegner scores. A significant improvement was noted in all clinical scores. In particular, the IKDC subjective score increased from 34.5±23.6 to 66.3±26.4 (P=.001). The Lysholm score showed a similar trend. From a baseline value of 47.8±29.5, the score increased to 79.8±24.6 at the last evaluation (P=.001). A significant increase in Tegner score was observed at the 2-year evaluation, with stable results up to the last follow-up. Four failures were reported, which in 3 cases occurred at mid- to long-term follow-up, confirming that this technique can be considered a suitable option for the treatment of small and medium chondral and osteochondral lesions in young patients.