The use of multiple autologous osteochondral plugs (mosaicplasty) for repair of articular cartilage defects is a well-accepted technique. Since 1995, the authors have used mosaicplasty to treat more than 110 patients with cartilage defects of the knee, hip, and ankle. The first 52 consecutive patients who had mosaicplasty of the knee and have an average followup of 37 months (range, 24–56 months) were examined. Indications for surgical treatment were osteochondritis dissecans, acute trauma, and posttraumatic lesions of the femorotibial joint, femoropatellar maltracking with recurrent episodes of patella dislocations, and distinct femoropatellar arthrosis. Preoperatively, cartilage defects were classified as International Cartilage Repair Society Grade III lesions in 23 patients and Grade IV lesions in 29 patients. Two years after surgery, an increased level of knee function was found in 86% of the patients. At the latest followup, improved knee function was observed in 92% of the patients. In four patients, reoperation was necessary because of graft failure. Complications and reoperation rate were related to large surface lesions. Autologous osteochondral transplantation is a valid option for the treatment of full-thickness osteochondral defects. However, the method is limited by the defect size and the number of plugs to be taken at the donor site.