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BACKGROUND Patients with spinal trauma are at high risk for venous thromboembolic events (VTE). Guidelines recommend prophylactic anticoagulation but they are unclear on timing of initiation of thromboprophylaxis. The aim of our study was to assess the impact of early versus late initiation of venous thromboprophylaxis in patients with spinal trauma who underwent operative intervention. METHODS We performed a 2-year (2013–2014) review of patients with isolated spine trauma (spine-Abbreviated Injury Scale score, ≥ 3 and no other injury in another body region with Abbreviated Injury Scale score, > 2) who underwent operative intervention and received thromboprophylaxis postoperatively. Patients were divided into two groups based on the timing of initiation of thromboprophylaxis: early(<48 hours) and late(≥48 hours), and were matched in a 1:1 ratio using propensity score matching for demographics, admission vitals, injury parameters, type of operative intervention, hospital course, and type of prophylaxis(low molecular weight heparin vs. unfractionated heparin). Outcomes were rates of deep vein thrombosis (DVT) and/or pulmonary embolism, red-cell transfusions, the rate of operative interventions for spinal cord decompression and mortality after initiation of thromboprophylaxis. RESULTS Nine thousand five hundred eighty-five patients underwent operative intervention and received anticoagulants, of which 3554 patients (early, 1,772; late, 1,772) were matched. Matched groups were similar in demographics, injury parameters, emergency department vitals, hospital length of stay, rates of inferior vena cava (IVC) filter placement and time to operative procedure. Patients who received thromboprophylaxis within 48 hours of operative intervention, unlike those who did not, were less likely to develop DVT (2.1% vs. 10.8%, p < 0. 01). However, the rate of pulmonary embolism was similar in both groups (p = 0.75). Additionally, there was no difference in postprophylaxis red cell transfusion requirements (p = 0.61), rate of postprophylaxis decompressive procedure on the spinal cord (p = 0.27), and mortality (p = 0.53). CONCLUSION Early VTE prophylaxis is associated with decreased rates of DVT in patients with operative spinal trauma without increasing the risk of bleeding and mortality. The VTE prophylaxis should be initiated within 48 hours of surgery to reduce the risk of DVT in this high-risk patient population. LEVEL OF EVIDENCE Therapeutic studies, level IV.