Despite the frequency and morbidity of venous thromboembolism (VTE) development after traumatic brain injury (TBI), no national standard of care exists to guide TBI caregivers for the use of prophylactic anticoagulation. Fears of iatrogenic propagation of intracranial hemorrhage patterns have led to a dearth of research in this field, and it is only relatively recently that studies dedicated to this question have been performed. These have generally been limited to retrospective and/or observational studies in which patients are classified in a binary fashion as having the presence or absence of intracranial blood. This methodology does not account for the fact that smaller injury patterns stabilize more rapidly, and thus may be able to safely tolerate earlier initiation of prophylactic anticoagulation than larger injury patterns. This review seeks to critically assess the literature on this question by examining the existing evidence on the safety and efficacy of pharmacologic VTE prophylaxis in the setting of elective craniotomy (as this is the closest model available from which to extrapolate) and after TBI. In doing so, we critique studies that approach TBI as a homogenous or a heterogenous study population. Finally, we propose our own theoretical protocol which stratifies patients into low, moderate, and high risk for the likelihood of natural progression of their hemorrhage pattern, and which allows one to tailor a unique VTE prophylaxis regimen to each individual arm.