Objective To evaluate effect and safety of first-line chemotherapy regimen combined with rh-endostatin for osteosarcoma of the extremities.Methods Sixty three patients with osteosarcoma were randomly divided into experiment group and control group.There were 32 patients in experiment group,and 31 patients in control group.Nine patients 9 were rejected because they did not meet the standard.Finally,54 patients were enrolled in this study,including 29 patients in experiment group,and 25 patients in control group.In the experiment group,the patients were treated with rh-endostatin combined with MTX,IFO,DDP,and ADM,while patients in control group were treated with MTX,IFO,DDP,and ADM.Several indexes including median progression-free survival time,clinical benefit rate,progression-free survival rate,limb salvage rate,and survival rate were used to assess clinical effect.The safety of rh-endostatin was evaluated by comparing incidence of adverse events in the two groups.Results The median progression-free survival time of experiment group and control group was 18.9 months and 13.1 months,respectively; there was no significant difference.In the experiment group,the clinical benefit rate,progression-free survival rate,survival rate and limb salvage rate were 89.7％,37.9％,65.5％,and 89.7％,respectively; while in the control group,the clinical benefit rate,progression-free survival rate,survival rate,and limb salvage rate were 88.0％,36.0％,68.0％,and 96.0％,respectively.There was no significant difference in 4 indexes mentioned above between two groups.Conclusion After being combined with first-line chemotherapy regimen,rh-endostatin doesn't show significant advantage in controlling tumour progression and improving survival rate.No more toxicity and new side effects are found after using rh-endostatin.