Objective <p>The pathophysiologic significance of transphyseal extension of pediatric osteosarcoma is unknown. The physis acts as a relative anatomic barrier to tumor extension and potentially to hematogenous spread. The purpose of this study was to determine whether transphyseal tumor extension on initial magnetic resonance imaging (MRI) correlates with metastatic disease.</p> Methods <p>This is a single-institution 13-year retrospective review of 269 patients aged ≤ 18&#xa0;years diagnosed with long bone osteosarcoma and open physes on pre-operative imaging. MRIs were reviewed to determine the presence of transphyseal tumor extension, skip lesions, pulmonary metastases, recurrence, and disease status at 3&#xa0;years. Univariable and multivariable analyses were performed.</p> Results <p>The final cohort included 109 patients (range 4–18&#xa0;years). Fifty-nine percent of patients had transphyseal tumor extension. In univariable analysis, pulmonary metastasis on initial chest CT was significantly higher in patients with transphyseal extension (32.8% vs 15.6%, <i>p</i> = .04). There was no evidence of a difference between patients with and without transphyseal extension with regard to skip lesions (15.6% vs 15.7%, <i>p</i> = .99), tumor recurrence (50% vs 44.4%, <i>p</i> = .57) or death alone (40.6% vs 26.7%, <i>p</i> = .13). Multivariable analysis accounting for age, sex, tumor location, and transphyseal extension demonstrated transphyseal extension to be independently associated with active disease or death by 3&#xa0;years (OR 3.26, <i>p</i> = 0.03).</p> Conclusion <p>Transphyseal tumor extension on initial MRI is associated with an increased prevalence of active disease/death at 3&#xa0;years follow-up. In addition to entire long bone MR imaging, dedicated high-resolution imaging to delineate transphyseal extension is recommended in the diagnostic workup of long bone osteosarcoma.</p>