BACKGROUND Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), remains a common complication following trauma. The role of hereditary thrombophilia (HT) in posttraumatic VTE is unknown. In the general population with a first-time DVT, Factor V Leiden (FVL) and prothrombin G20210A mutation (PGM) are the most common types of HT with an incidence of 20% to 25% and 6% to 18%, respectively. The objective of this study was to identify the incidence of FVL and PGM in posttraumatic VTE to determine whether routine screening for HT in trauma should be performed. METHODS We conducted a prospective observational study at our Level I trauma center from 2013 to 2016 when 70 patients with posttraumatic DVT and PE were screened for FVL and PGM. Demographics, injury characteristics, and established risk factors for VTE were collected for each patient. Statistical analysis was performed to compare patients with and without HT. RESULTS The incidence of FVL and PGM in posttraumatic VTE was 1.4% and 5.7%, respectively. All HT-positive patients had a DVT and one had an associated PE. Both the individual risk factors and the total number of risk factors for VTE were similar between the HT-positive group and the HT-negative group. CONCLUSION There was a lower incidence of FVL and PGM in patients with posttraumatic DVT than in patients with a first-time DVT in the general population. HT does not appear to significantly contribute to posttraumatic VTE in our trauma population. Further research is warranted to determine whether routine screening for HT in trauma should be performed. LEVEL OF EVIDENCE Epidemiological study, level III; Care management/therapeutic study, level IV.