Background: Patients suffering from traumatic brain injury (TBI) are at increased risk of venous thromboembolism (VTE). However, initiation of chemoprophylaxis (VTEp) may cause further intracranial hemorrhage. We reviewed the literature to determine the post-injury time interval at which VTEp can be administered without risk of TBI evolution and hematoma expansion. Methods: MEDLINE and EMBASE databases were searched. Inclusion criteria were: studies investigating timing and safety of VTEp in TBI patients not previously on oral anticoagulation. Two investigators extracted data and graded the papers based on levels of evidence. Results: A total of 408 studies were screened. Forty-five studies were reviewed in-entirety and 21 were included in the systematic review. There were 2 prospective randomized trials and 19 comparative studies. Eighteen total studies demonstrated that VTEp post injury in patients with stable head computed tomography scan does not lead to TBI progression. Fourteen studies demonstrated that VTEp administration specifically 24–72 hours post injury is safe in patients with stable injury. Four studies suggested that administering VTEp within 24 hours of injury in patients with stable TBI does not lead to progressive ICH. Conclusions: Literature suggests that administering VTEp 48 hours post-injury may be safe for patients with low-hemorrhagic risk TBIs and stable injury on repeat imaging.