Background: Pulmonary metastasectomy is considered a necessary component of curative therapy in pulmonary metastatic osteosarcoma, however the optimal surgical approach is unknown. Two approaches include open surgery (OSY) including thoracotomy or sternotomy and minimally invasive surgery (MSY) by thoracoscopy. No randomized trial has been completed comparing these approaches in patients with osteosarcoma, however randomized controlled trials in other cancers have not identified superior outcomes in patients undergoing OSY. OSY allows for direct palpation of all lung surfaces and more pulmonary metastatic nodules can be identified during OSY compared to the number predicted by pre-operative imaging. MSY offers the benefit of faster patient recovery, improved quality of life and potential for equivalent surgical control of relevant metastatic disease. Given wide variability in surgical approach and willingness of both surgical oncology and patient advocacy communities to participate in a randomized trial, AOST2031 was developed to address this clinical equipoise. Methods: Eligibility for AOST2031 includes patients < 50 yrs with a histological diagnosis of osteosarcoma and evidence of pulmonary metastases at initial diagnosis or at first recurrence. Patients must have oligometastatic lung metastasis considered resectable by either OSY or MSY, with rapid central review of chest CT images to confirm eligibility. Systemic therapy considered equivalent to methotrexate, cisplatin and doxorubicin is required to be ongoing in newly diagnosed and completed in patients with recurrence. Exclusion criteria include unresectable primary disease, metastatic disease requiring anatomic lung resection, pleural or mediastinal lesions or pleural effusions, progression while receiving initial therapy, extra-pulmonary metastases and prior chest surgery for pulmonary metastases. Patients are randomized 1:1 to either OSY or MSY, with randomization stratified by disease status and risk. The primary outcome is thoracic event free survival, defined as intrathoracic tumor recurrence or death that results from the procedure or a complication related to the procedure. Two-hundred and twenty-five eligible patients are anticipated to answer the primary objective. Secondary objectives include event free, overall survival and . Exploratory objectives include surgical complication rates, patterns of recurrence, use of surgical localization techniques, comparison of CT findings to pathology of resected specimens, and patient reported outcomes. Biologic objectives include the collection of metastatic tissues to facilitate the study of metastatic disease and serial blood samples for future tumor profiling, germline and circulating tumor DNA studies. AOST2031 opened to enrollment at NCTN sites in February 2022. Clinical trial information: NCT05235165.