Background: Osteosarcoma (OS) has a peak incidence amongst adolescents and young adults (AYA). Nuances in chemotherapeutic regimens are largely influenced by the training of pediatric or medical oncologists. MAP is the standard chemotherapy regimen used by pediatric oncologists. Chemotherapy regimens used by medical oncologists vary; our center uses preoperative doxorubicin/cisplatin (AP) followed by either doxorubicin/ifosfamide (AI) or a combination of HD methotrexate and HD ifosfamide. We undertook this analysis to characterize the treatment response, toxicity, and survival outcomes for AYAs with OS treated with pediatric vs medical oncology regimens as an initial step towards harmonizing our institutional approach to the treatment of AYA patients with bone sarcomas. Methods: We retrospectively reviewed the records of AYAs with OS receiving primary treatment at our center. Clinicopathologic characteristics and outcomes for patients treated with MAP vs. AP+ were compared. Progression-free survival (PFS) was defined as the time from either MAP/AP+ initiation or surgery to the time of first recurrence or death. Overall survival was defined as the time from MAP/AP+ initiation or surgery to death. The distributions of PFS and overall survival were estimated by the Kaplan-Meier method. Log-rank test was performed to test the difference in survival between groups. Regression analyses of survival data based on the Cox proportional hazard (PH) model were conducted on the time to event outcomes. Results: Between 2016-2022, 209 OS patients were seen at our center for initial diagnosis and treatment recommendations including 124 AYAs (59%). Amongst AYAs, 41 patients (median age 22y, range 14-38y) initiated and received the majority of their chemotherapy at our center and were included in analysis. Of the 41 AYAs, 17 were treated on MAP; 24 were treated using AP+. Ten patients < 20 years received MAP; one patient >30 years received MAP. The median time from initiation of therapy to surgery for those receiving MAP was 87.5 days vs 95.5 days for AP (p = 0.0052). Percent tumor necrosis varied widely with both regimens (range 0-99%) and was not statistically different (p = 0.11). There was no statistically significant difference in PFS between AYAs treated with MAP as compared to AP+ (Three-year PFS rates 80% vs 66%, p = 0.40). Evaluation of treatment related toxicity and late effects is ongoing. Conclusions: We had insufficient data to compare survival outcomes in this limited retrospective series. This limited retrospective study did not show a statistically significant difference in PFS for AYA patients with OS treated with a standard pediatric vs. adult type regimen containing at least 3-drug chemotherapy. Further study is needed to refine treatment for this patient population. These data support prospective efforts to harmonize AYA treatment paradigms in osteosarcoma.