Background: A factor-based coagulation management following major trauma is recommended as standard of care by the European Trauma Treatment Guidelines. However, concerns about the thromboembolic risk of this approach are still prevalent. Our study therefore aims to assess if such a haemostatic management is associated with an increased risk for thromboembolic events. Methods: In this retrospective observational study carried out at the University Hospital Zurich we compared two three-year periods before (period 1: 2005-2007) and after (period 2: 2012-2014) implementation of a factor-based coagulation algorithm. We included all adult patients following major trauma primarily admitted to the University Hospital Zurich. Thromboembolic events were defined as a new in-hospital appearance of any peripheral thrombosis, arterial embolism, pulmonary embolism, stroke or myocardial infarction. A logistic regression was performed to investigate the association of thromboembolic events with possible confounders such as age, sex, specific Abbreviated Injury Scale (AIS) subgroups, allogeneic blood products, and the coagulation management. Results: Out of 1138 patients, 772 met the inclusion criteria: 344 patients in period 1 and 428 patients in period 2. Thromboembolic events were present in 25 patients (7.3%) of period 1 and in 42 patients (9.8%) of period 2 (raw OR 1.39, 95% CI 0.83 to 2.33, p = 0.21). Only AIS extremities (adjusted OR 1.26, 95% CI 1.05 to 1.52, p = 0.015) and exposure to allogeneic blood products (adjusted OR 2.39, 95% CI 1.33 to 4.30, p = 0.004) were independently associated with thromboembolic events in the logistic regression, but the factor-based coagulation management was not (adjusted OR 1.60, 95% CI 0.90-2.86, p = 0.11). Conclusion: There is no evidence that a goal-directed, factor-based coagulation management is associated with an increased risk for thromboembolic events following major trauma.