Members of AKT kinase family are central modulators in numerous signaling cascades, which regulate metabolism, cell proliferation, survival and growth. Previously, the knockdown of AKT2 expression has been demonstrated to enhance the efficacy of chemotherapy in patients with osteosarcoma. However, it is currently unknown whether the aberrant expression of AKT2 has relevance to the progression of osteosarcoma. The aim of the present study was to investigate the clinicopathological and prognostic value of AKT2 in osteosarcoma. Formalin-fixed paraffin embedded osteosarcoma and self-paired non-cancerous bone tissue samples were obtained from 126 patients with osteosarcomas. AKT2 expression was detected by an immunohistochemistry assay. Patient survival rates were determined by the Kaplan-Meier method and log-rank test. Cox regression was adopted for multivariate analysis of the prognostic factors to examine the effect of AKT on event-free survival and overall survival in patients with osteosarcomas. AKT2 expression in osteosarcoma tissues was significantly higher than that in non-cancerous bone tissues (immunostaining score, 6.39±1.62 vs. 3.46±1.03; P<0.001). In addition, the elevated expression of AKT2 protein was significantly associated with positive recurrence (P=0.023), the presence of metastasis (P=0.006) and poor response to chemotherapy (P=0.015). Furthermore, patients with high AKT2 expression had significantly shorter event-free survival (P<0.001) and overall survival times (P<0.001) than those with lower expression levels. Multivariate analysis further demonstrated that AKT2 expression (P=0.029 and 0.016, respectively), the status of recurrence (P=0.018 and 0.012, respectively) and metastasis (P=0.020 and 0.015, respectively), and the response to chemotherapy (P=0.011 and 0.008, respectively) were all independent prognostic factors for event-free survival and overall survival time. To the best of our knowledge, these data have supported the findings for the first time, that the elevated expression of AKT2 may be associated with aggressive clinical behavior and poor outcome in patients with osteosarcomas. Therefore, AKT2 may be a candidate marker of unfavorable prognosis in osteosarcoma.