The purpose of this study was to prospectively evaluate the use of ultrasonographically guided high-intensity focused ultrasound (HIFU) in the salvage of limbs in patients with osteosarcoma. Seven patients underwent HIFU ablation. Laboratory and radiologic examinations were performed after intervention. Changes in symptoms and survival time were noted at follow-up. No severe complications were observed, and preexisting severe pain disappeared in patients treated with HIFU. Alkaline phosphatase did not show statistically significant changes before and after HIFU treatment, although Alkaline phosphatase did change 1 mo and 2 mo after HIFU. Complete response of the tumor was achieved in three patients with osteosarcoma. Partial response was achieved in another three patients treated with HIFU. Pulmonary metastasis was noted in only one patient 5 mo after HIFU. The median survival time was 68 mo. All patients were alive 3 y after HIFU treatment. Five patients were alive at follow-up visits after 5 y. One patient died from cachexia and infection after 4 y, another patient died of cardiac arrest attack after 4 y. Three patients died of lung dysfunction from pulmonary metastases after 5 y. The five-year survival rate was 71.4%. The authors concluded that HIFU ablation was a safe and feasible method of treatment of osteosarcoma which salvages the limb, but large-scale randomized clinical trials are necessary for confirmation.