Recently, apatinib has been shown to be effective in treating sarcoma. This study aimed to assess the safety and efficacy of apatinib in the treatment of patients with osteosarcoma after failed of standard multimodal therapy and to compare the therapeutic effects of apatinib on osteosarcoma between high-dose group and low-dose group.A total of 27 patients with osteosarcoma who received apatinib between January 2016 and August 2017 were retrospectively reviewed. Among the 27 patients, the objective response rate (ORR) and the disease control rate (DCR) were 25.93% and 66.67%, respectively. The median of progression-free survival (m-PFS) was 3.5 months (95% confidence interval [CI], 2.5-4.8 months), and the median of overall survival (m-OS) was 9.5 months (95% CI, 7.8-10.5 months). There was no statistically significant difference in ORR (36.36% vs 18.75%), DCR (63.64% vs 68.75%), m-PFS (4.3 months [95% CI, 1.8-7 months) vs 3.35 months (95% CI, 1.8-4 months]), and m-OS (9.5 months [95% CI, 7.8-10.5 months] vs 9.4 months [95% CI, 7.8-10.8 months]) (P > .05) between the high-dose group (the average dose was 659 mg/qd) and the low-dose group (the average dose was 516 mg/qd). Most of the adverse events (AEs) were in grade 1 or grade 2. The main AEs in grade 3 were hypertension, rash, weight loss, hand-foot syndrome, and diarrhea.Apatinib is safe and effective in the treatment of advanced osteosarcoma. We recommend that the initial dose of apatinib should be 500 mg/qd in the treatment of osteosarcoma.