PURPOSE: To improve survival rates and functional outcome in patients with non-metastatic, high-grade osteosarcoma of the extremities, using the Scandinavian Sarcoma Group XIV neoadjuvant chemotherapy protocol. PATIENTS AND METHODS: The analysis included 37 patients treated during the period 2000-2005. Age range was 8 to 65 year (median 23). Seven (7/37) patients were excluded from the study. The remaining 30 patients received 2 cycles of preoperative chemotherapy (high dose methotrexate, cisplatin and doxorubicin). Surgery was carried out in the 9th week. Twenty-seven (90%) patients had limb-salvage operation and in the remaining 3 amputation was performed. Based on the histopathological assessment of the removed tumor patients were classified in two groups (regarding good or poor response to chemotherapy). All 30 patients received 3 courses of postoperative chemotherapy with the same regimen. Patients with poor response received 3 more cycles of chemotherapy with high dose ifosfamide. Follow-up was 2-8 years (mean 52 months). RESULTS: Histopathological assessment showed poor response to neoadjuvant chemotherapy in 57% of the patients but no significant difference in 3-year survival between the 2 groups was noted. Three-year survival of the patients with local recurrence was 40 vs. 88% of those without local recurrence (p=0.013). Three-year survival of the patients with distant metastases was 20 vs. 92% of those without distant metastases (p=0.0002). Three-year overall survival (OS) was 80% and disease-free survival (DFS) 60% for all 30 patients. CONCLUSION: Neoadjuvant chemotherapy in patients with high-grade osteosarcoma of the extremities gives the opportunity for limb-sparing operation and at the same time improves survival rates.