Upregulation of a disintegrin and metalloprotease 8 influences tumor metastasis and prognosis in patients with osteosarcoma. To investigate the clinicopathological and prognostic value of a disintegrin and metalloprotease 8 (ADAM8) in osteosarcoma. ADAM8 expression in osteosarcoma tissues was examined by immunohistochemistry in 69 patients. ADAM8 was positively expressed in 61 of 69 (88.4%) osteosarcoma specimens with cytoplasmic staining, and also increased in the specimens with recurrence (P = 0.008) and metastasis (P = 0.002). Patients with strong ADAM8 expression had significantly poorer overall survival (OS) and disease-free survival (DFS) (both P < 0.001) when compared with the patients with the weak expression of ADAM8. On multivariate analysis, ADAM8 expression was found to be an independent prognostic factor for both OS (P < 0.001) and DFS (P < 0.001). Our results suggest for the first time that ADAM8 might be applied as a novel marker for the prediction of recurrence and metastasis potency and a significant indicator of poor prognosis for patients with osteosarcoma.