OBJECTIVE To evaluate the clinical efficacy of neoadjuvant chemotherapy for treating osteosarcoma. METHODS 102 osteosarcoma patients in our hospital were randomly assigned into the neoadjuvant chemotherapy group and the surgery group. Patients in the chemotherapy group received neoadjuvant chemotherapy after pathological diagnosis. Surgery was performed 3 weeks after chemotherapy, followed by 4-6 cycles of postoperative chemotherapy. Osteosarcoma patients in the surgery group were operated once diagnosed and received no chemotherapy. Limb salvage or amputation surgery were performed according to the boundary of tumor resection. All patients were followed up for 24 months. The clinical efficacy, limb function, disease-free survival (DFS) and incidence of adverse events were compared between the two groups. RESULTS Limb salvage rate and disease control survival in the chemotherapy group were higher than those of the surgery group (p<0.05). After follow up for 24 months, the 2-year DFS in the chemotherapy group was remarkably prolonged compared to the surgery group (p<0.05). No significant differences in the incidence of adverse events were observed between both groups (p>0.05). Limb function was markedly improved in the chemotherapy group compared with that of the surgery group. CONCLUSIONS Preoperative neoadjuvant chemotherapy for treating osteosarcoma remarkably improves the limb salvage rate, disease control rate and overall survival (OS), and constitutes an effective and safe option for osteosarcoma patients.