Background: Venous thromboembolism (VTE) is a serious complication following severe TBI, however, anticoagulant prophylaxis is often withheld over concerns of intracranial hemorrhage (ICH) progression. We analyzed practice patterns and outcomes among severe TBI patients and systematically reviewed the literature for studies of anticoagulant prophylaxis after severe TBI. Methods: We prospectively screened consecutive patients with severe TBI (highest GCS≤8 from time of injury to ICU admission) admitted to a Level-I trauma centre between Oct 1,2015–Sept 30,2016 to assess type/timing of anticoagulant prophylaxis, rates of new VTE and ICH progression. Results: We identified 64 eligible patients with severe TBI. Most (53;83%) received anticoagulant prophylaxis, initiated ≥3d after TBI in 67%. Ten (16%) developed VTE during hospitalization; 8 started prophylaxis prior to VTE. No significant difference was observed in VTE incidence or ICH progression between patients with early prophylaxis (<3d) vs.later (≥3d). Our systematic review identified 5 studies of heterogeneous quality/design, with reported VTE incidence of 11-30% in patients without anticoagulant prophylaxis and 5-10% in patients with prophylaxis. Conclusions: VTE is a common complication after severe TBI despite routine use of anticoagulant prophylaxis. Anticoagulant prophylaxis is often started late (≥3d) post-injury. The relative benefits of early prophylaxis versus possible risks of ICH progression should be directly compared in an appropriately powered RCT.