Abstract: Objective To investigate the efficacy and side effects of two combinations of highdose methotrexate（MTX）， cisplatin（DDP）， adriamycin（ADM） and ifosfamide（IFO） in the treatment of extremity osteosarcoma patients with stage ⅡB. Methods A retrospective analysis was conducted for 185 osteosarcoma patients treated with the four drugs mentioned above. Ninety three patients received the Italian therapeutic scheme IOR-OS／N-5（MTX 812g／m²iv 6h，d₁，CF 15mg at one time，12 times；DDP 80-100mg／m²，ADM 60mg／m² iv，d8；IFO 20g／m2iv d21d25，mesna 400mg after IFO for 0，4，8h）and the remaining 92 patients received the therapeutic scheme optimized（MTX 812g／m2iv 6h，d1，CF 15mg at one time，12times；DDP 80-100mg／m² iv，d₈；ADM 60mg／m² iv d₂₁，IFO 2.0g／m²iv d₂₁-d₂₅，mesna 400mg after IFO for 0，4，8h）. To compare the efficacy and side effects of two therapeutic schemes. Results The limb salvage rates of IOROS／N-5 and optimized schemes were 52.7％（49／93）and 58.7％（54／92）， respectively. The 3-year recurrence rates of IOR-OS／N-5 and optimized schemes were 14.0％ and 7.6％，respectively. The 3-year metastasis rates of IOR-OS／N-5 and optimized schemes were 47.3％ and 30.4％， respectively. The 3-year survival rates of IOR-OS／N-5 and optimized schemes were 57.0％ and 75.0％ with statistical significance（P＜0.05）. The median diseasefree survival times of two groups were 22.2 months（95％CI：16.2-28.2）and 29.0 months（95％CI：23.8-34.3），respectively. There was statistical significance（P=0.024）.The median overall survival times of two groups were 32.2 months（95％CI：23.2-38.2） and 36.1 months（95％CI：33.8-44.3），respectively. There was statistical significance（P=0.032）. The main side effects were liver function damages， myelosuppression， nausea and vomiting and so on. The incidence rate of liver damage with grade 3-4 accounted for 35.2％ and 16.6％ in IOR-OS／N-5 and optimized scheme groups， respectively. Grade 3-4 neutropenia accounted for 22.6％ and 30.2％ in two groups， respectively. Conclusion Optimization of highdose MTX， DDP， ADM and IFO based on the Chinese patients body condition increases the resistance and efficacy in the treatment of osteosarcoma.