Various studies examining the relationship between Ezrin overexpression and response to chemotherapy and clinical outcome in patients with osteosarcoma have yielded inconclusive results. We accordingly conducted a meta-analysis of 7 studies (n = 318 patients) that evaluated the correlation between Ezrin and histologic response to chemotherapy and clinical prognosis (death). Data were synthesized in receiver operating characteristic curves and with fixed-effects and random-effects likelihood ratios and risk ratios. Quantitative synthesis showed that Ezrin is not a prognostic factor for the response to chemotherapy. The positive likelihood ratio was 0.538 (95% confidence interval [95% CI], 0.296- 0.979; random-effects calculation), and the negative likelihood ratio was 2.151 (95% CI, 0.905- 5.114; random-effects calculations). There was some between-study heterogeneity, but no study showed strong discriminating ability. Conversely, Ezrin positive status tended to be associated with a lower 2-year survival (risk ratio, 2.45; 95% CI, 1.26-4.76; random-effects calculation) with some between-study heterogeneity that disappeared when only studies that employed immunohistochemistry were considered (risk ratio, 2.97; 95% CI, 2.01- 4.40; fixed-effects calculation). To conclude, Ezrin is not associated with the histologic response to chemotherapy in patients with osteosarcoma, whereas Ezrin positivity was associated with a lower 2-year survival rate regarding risk of death at 2 years. Expression change of Ezrin is an independent prognostic factor in patients with osteosarcoma.