Background Although pre-injury antithrombotic agents, including antiplatelets and anticoagulants, are historically associated with expansion of traumatic intraparenchymal hemorrhage (tIPH), the literature has poorly elucidated the actual risk of hematoma expansion on repeat computed tomography (CT). The objective was to determine the effect of antithrombotic agents on hematoma expansion in tIPH by comparing patients with and without pre-injury antithrombotic medication. Methods The volume of all tIPHs over a 5-year period at an academic Level 1 trauma center was measured retrospectively. The initial tIPH was divided into 3 equally sized quantiles. The third tercile, representing the largest subset of tIPH, was then removed from the study population because these patients reflect a different pathophysiologic mechanism that may require a more acute and aggressive level of care with reversal agents and/or operative management. Per institutional policy, all patients with small- to moderate-sized hemorrhages received a 24-hour stability CT scan. Patients who received reversal agents were excluded. Results Of the 105 patients with a tIPH on the initial head CT scan, small- to moderate-sized hemorrhages were Conclusions In small- to moderate-sized tIPH, withholding antithrombotic agents without reversal may be sufficient.