OBJECTIVE Maximal safe resection is the standard-of-care treatment for adults with intracranial ependymoma. The value of adjuvant radiotherapy remains unclear as these tumors are rare and current data are limited to a few retrospective cohort studies. In this study, the authors assembled a cohort of patients across multiple international institutions to assess the utility of adjuvant radiotherapy in this patient population. METHODS Adults with intracranial ependymoma managed surgically at the University Health Network in Toronto, Canada, the University of Oklahoma Health Sciences Center in Oklahoma City, Oklahoma, and The Ottawa Hospital in Ottawa, Canada, were included in this study. The primary end points were progression-free survival (PFS) and overall survival (OS). Clinicopathological variables were assessed in univariate and multivariate Cox proportional hazard models for prognostic significance of PFS and OS. RESULTS A total of 122 patients diagnosed between 1968 and 2019 were identified for inclusion. The majority of patients had grade II ependymomas on histopathology (78%) that were infratentorially located (71%), underwent gross-total (GTR) or near-total resection (NTR; 55%), and were treated with adjuvant radiotherapy (67%). A volumetric analysis of the extent of resection in 49 patients with available tumor volume data supported the accuracy of the categorical GTR, NTR, and subtotal resection (STR) groups utilized. Independent statistically significant predictors of poorer PFS in the multivariate analysis included STR or biopsy (vs GTR/NTR; HR 5.4, 95% confidence interval [CI] 2.4–11.0, p < 0.0001) and not receiving adjuvant radiotherapy; cranial (HR 0.5, 95% CI 0.2–1.1) and craniospinal (HR 0.2, 95% CI 0.04–0.5) adjuvant radiotherapy regimens improved PFS (p = 0.0147). Predictors of poorer OS in the multivariate analysis were grade III histopathology (vs grade II: HR 5.7, 95% CI 1.6–20.2, p = 0.0064) and undergoing a biopsy/STR (vs GTR/NTR: HR 9.8, 95% CI 3.2–30.1, p = 0.0001). CONCLUSIONS The results of this 50-year experience in treating adult intracranial ependymomas confirm an important role for maximal safe resection (ideally GTR or NTR) and demonstrate that adjuvant radiotherapy improves PFS. This work will guide future studies as testing for molecular ependymoma alterations become incorporated into routine clinical practice.