Background: Chemotherapy in the treatment of osteosarcoma has improved 5 year overall survival (OS) from 20% with surgery alone to 60-70%. However, poor tumor necrosis following neoadjuvant chemotherapy (NAC) is associated with decreased survival, therefore strategies to improve outcomes are required for these patients. Methods: Records from all adult patients diagnosed with osteosarcoma between 1986 and 2012 were retrospectively reviewed. Patients were stratified according to age at diagnosis (<40yrs and >40yrs), stage (localised or metastatic) and tumor necrosis post NAC (<90% and >90%). All patients received 2 cycles of methotrexate alternating with cisplatin/doxorubicin (MAP) preoperatively. Following surgery, patients with >90% tumor necrosis continued MAP whilst those with <90% necrosis switched to 4 cycles of ifosfamide and etoposide (IE). Results: 105 patients were identified and 98 who received systemic chemotherapy were included. Median age was 23yrs (Range 15-75yrs); 68% of patients were male. Limb sparing surgery was performed in 76% of applicable patients. Of the patients with localised disease (N=85), 5 year OS, with a median follow up of 8 years (1-26 yrs) was 68% (p=0.002). Patients <40 yrs with localised disease had a 5yr OS of 71% (N=73) compared to 40% in those >40 yrs (N=12) (p=0.05). 2/13 patients with metastatic disease at diagnosis are disease free >10 years post diagnosis. 65 of 73 patients with localised disease < 40 yrs had histology reviewed post neoadjuvant MAP. 34/65 (52%) had >90% tumor necrosis and continued on MAP, 5 yr OS 79%, 31 patients (48%) had <90% necrosis and received adjuvant IE, 5 yr OS 68% (P=0.10). Conclusions: Age and stage are important prognostic factors in patients with osteosarcoma treated with chemotherapy and surgery. Historically, patients with <90% tumor necrosis post NAC are considered to have a poorer prognosis. Switching from MAP to IE is an appropriate salvage regimen in such patients and appears to improve long term survival.