The aim of this retrospective, multicenter study was to evaluate clinicopathological characteristics, prognostic factors and treatment outcomes of teenage and adult patients with high-grade osteosarcoma. A total of 240 osteosarcoma patients who were diagnosed and treated from March 1995 to September 2011 were analyzed. Median age was 20 years (range 13-74 years), and 153 patients (63.8%) were male. Primary tumor localization was extremity in 204 patients (85.4 %), trunk in 21 patients (8.8%) and head and neck region in 14 patients (5.9%). According to American Joint Committee on Cancer staging system, 186 patients (77.5%) were stage II, 3 (1.3%) were stage III and 48 (20.0%) were stage IV. Median overall survival (OS) was 55 months (95 % CI 36.8-73.1 months). OS after 2, 5 and 10 years were 67, 49 and 42%, respectively. Univariable analysis for OS showed that male gender (p = 0.032), high baseline lactate dehydrogenase (LDH) level (p < 0.001), high baseline serum alkaline phosphatase level (p = 0.002), telangiectatic subtype (p = 0.023), presence of metastasis at diagnosis (p < 0.001), presence of tumor positive margins after primary surgery (p = 0.015), poor pathological response to preoperative chemotherapy (p = 0.006) and presence of recurrent disease during follow-up period (p < 0.001) were significantly associated with poor survival. Patients who received postoperative methotrexate plus doxorubicin plus cisplatin (M + A + P) combination regimen (p = 0.019), underwent surgery for recurrent disease (p < 0.001) and received chemotherapy for recurrent disease (p < 0.001) had longer OS. In multivariable analysis for OS, only high LDH level (p = 0.002) and the presence of metastasis at diagnosis (p = 0.011) were associated with poor OS, whereas the patients who received chemotherapy for recurrent disease had a longer OS (p = 0.009).