BACKGROUND: Venous thromboembolism (VTE) remains a major source of morbidity and mortality in severely injured patients despite current methods of risk stratification and prophylaxis, suggesting incomplete understanding of VTE risk factors. Given the liver's role in coagulation, we hypothesized that liver injury (LI) is associated with increased rates of VTE in severely injured patients. STUDY DESIGN: The American College of Surgeons TQIP 2017 to 2021 was retrospectively reviewed for patients with a maximum abdominal Abbreviated Injury Score 4 or more with or without LI. Transfers, burns, all kinds of death, and patients younger than 18 years of age were excluded. Logistic regression was performed to assess the independent effect of LI on development of pulmonary embolism (PE) and deep venous thrombosis (DVT) while controlling for potential confounding variables. RESULTS: Of 44,506 patients, there were 1,736 (3.9%), 890 (2.0%), and 18,642 (41.9%) with DVT, PE, and LI, respectively. After controlling for potential confounders, LI was independently associated with PE (adjusted odds ratio 1.279, 95% CI 1.088 to 1.504) but was not associated with DVT (adjusted odds ratio 1.011, 95% CI 0.897 to 1.140). CONCLUSIONS: In severely injured patients, LI is an independent predictor of PE, but not DVT, suggesting that LI is the source of either emboli or a more complex locally prothrombotic focus leading to downstream thrombi in the lung without causing upstream systemic venous thrombi. Further work should focus on elucidation of mechanisms including the portal venous blood coagulation profile, endothelial injury in the liver, and the potential for stasis of venous blood traversing an injured liver as well as the role for including LI in VTE risk stratification.