Seven randomized controlled trials with 2,529 patients with histologically confirmed osteosarcoma were included in this meta-analysis. The purpose of this study was to compare the safety and efficacy of ifosfamide-based chemotherapy to a control group receiving chemotherapy without ifosfamide. The results displayed that ifosfamide-based chemotherapy had significantly higher event-free survival, overall survival, and good histologic response rates compared to the control groups. Prognostic variables were not shown to influence event-free survival and ifosfamide treatment resulted in higher incidences of fever and required more frequent platelet transfusion.