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Hemorrhage volume is an important variable in emergently assessing traumatic brain injury (TBI). The most widely used method for rapid volume estimation is ABC/2, a simple algorithm that approximates lesion geometry as perfectly ellipsoid. The relative prognostic value of volume measurement based on more precise hematoma topology remains unknown. In this study, we compare volume measurements obtained using ABC/2 versus computer-assisted volumetry (CAV) for both intra- and extra-axial traumatic hemorrhages, and then quantify the association of measurements using both methods with patient outcome following moderate to severe TBI. A total of 517 computer tomography (CT) scans acquired during the Progesterone for Traumatic Brain Injury Experimental Clinical Treatment Phase-III (ProTECTIII) multi-center trial were retrospectively reviewed. Lesion volumes were measured using ABC/2 and CAV. Agreement between methods was tested using Bland–Altman analysis. Relationship of volume measurements with 6-month mortality, Extended Glasgow Outcome Scale (GOS-E), and Disability Rating Scale (DRS) were assessed using linear regression and area under the curve (AUC) analysis. In subdural hematoma (SDH) >50cm3, ABC/2 and CAV produce significantly different volume measurements (p < 0.0001), although the difference was not significant for smaller SDH or intra-axial lesions. The disparity between ABC/2 and CAV measurements varied significantly with hematoma size for both intra- and extra-axial lesions (p < 0.0001). Across all lesions, volume was significantly associated with outcome using either method (p < 0.001), but CAV measurement was a significantly better predictor of outcome than ABC/2 estimation for SDH. Among large traumatic SDH, ABC/2 significantly overestimates lesion volume compared with measurement based on precise bleed topology. CAV also offers significantly better prediction of patient functional outcofme and mortality. [ABSTRACT FROM AUTHOR]