BACKGROUND Since the first trial for chemotherapy in children with osteosarcoma in 1977, the survival rate has gradually improved. Currently, more than 60% of all patients are cured, mainly because of the introduction of intensive chemotherapy using doxorubicin, high dose methotrexate, and cisplatin. The increased survival rates have promoted efforts to improve the quality of survival through the use of limb salvage surgery rather than amputation. Improvements in chemotherapeutic efficacy should result in a more favorable outcome and better function of the affected limb. The current study evaluated factors that influence chemotherapy so that a higher survival rate could be obtained. METHODS Three chemotherapy regimens comprised of doxorubicin, high dose methotrexate, cisplatin, and ifosfamide were retrospectively analyzed in 67 pediatric osteosarcoma patients. Twenty-three patients were treated with chemotherapy comprised of high dose methotrexate and doxorubicin (OOS-A regimen), 25 were treated with OOS-A with the addition of cisplatin (OOS-B), and 19 were treated with OOS-B with the addition of ifosfamide (OOS-C). RESULTS The OOS-A regimen was poorest in terms of survival (40.6%) compared with the OOS-B (67.5%) and OOS-C regimens (72.5%) (P < 0.001). There was no significant difference in survival between the OOS-B and OOS-C regimens. In the OOS-B regimen, patients who received a higher relative dose intensity showed a better prognosis. CONCLUSIONS These findings show that doxorubicin, high dose methotrexate, and cisplatin are the most potent drugs and suggest that it is more important to maintain the dose intensity of the regimen to improve survival rather than add a new drug.