Background: This prospective study assessed the efficacy of neoadjuvant and adjuvant chemotherapy on patients with high risk soft tissue sarcomasof the extremities.Methods: Enrolled patients received the following neoadjuvant chemotherapy: doxorubicin (75 mg/m2) on day1, ifosfamide (2.5 g/m2/d) and mesna (20% of the ifosfamide dose) from days1 to 3, repeated every three weeks for a total of three cycles, followed by surgery and radiotherapy. Patients received an additional three cycles of adjuvant chemotherapy that was the same as the neoadjuvant protocol following completion of radiotherapy.Results: There were 52 patients enrolled in the study, of which 50 were included in data analysis. Neoadjuvant chemotherapy was completed by 90% of enrolled patients and 88% completed all planned chemotherapy. A total of 96% of patients underwent surgery and 92% of these had R0 resections. Postoperative radiotherapy was administered to 96% of patients. The estimated three-year local-regional failure was 10%. Estimated three-year rate for distant disease-free survival was 66% and overall survival was 88%. One patient died with treatment secondary to leukopenic sepsis and respiratory failure. Grades 3-4 toxicities were experienced by 86% of patients of which 84% were grades 3- 4 hematologic toxicities and 38% were grades 3-4 non- hematologic toxicities.Conclusion: The current protocol is feasible and associated with favorable distant disease-free survival, overall survival, and limb preservation. This protocol is tolerable and has a manageable toxicity level.