Absent pupillary reaction occasionally heralds a poor prognosis following severe head injury. The purpose of the study was to evaluate the outcome of all patients who underwent acute evacuation of epidural hematoma (EDH) despite absent bilateral pupillary reaction. The Trauma Quality Improvement Program (TQIP) database for the calendar years 2017 and 2018 was accessed for the study. Adult patients ≥18 years of age who sustained severe traumatic brain injury (TBI) with the diagnosis of EDH and underwent evacuation of the hematoma were included in the study. The patients' characteristics, injury severity score (ISS), Glasgow Coma Scale (GCS) score, midline shift, and comorbidities were compared between patients who had absence of both pupillary reaction (ABPR) and those who presented with presence of both pupillary reaction (PBPR). The primary outcome of the study was in-hospital mortality. Propensity score matching analyses were performed for the study. No significant differences were found between the ABPR and PBPR groups regarding the median age (37 years [interquartile range (IQR): 26-53] vs. 40 years [IQR: 28-55]), gender (males; 81.9 vs. 79.5%), median ISS (29 [25.5-34] vs. 27 [25-33]), GCS score (3 [3-4] vs. 3 [3-3], presence of significant midline shift (75.9 vs. 79.5%), and comorbidities. The patients who presented with ABPR had a significantly higher mortality (34.9 vs. 10.8%; p = 0.002). A higher number of patients were discharged to skilled nursing and rehabilitation facilities (16.7 vs. 10.8% and 46.3 vs. 41.9%, respectively; p = 0.045). Approximately 65% of severe TBI patients survived after the evacuation of the EDH despite the absence of pupillary reaction.