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Background: Venous thromboembolism (VTE) is one of the most common preventable causes of in-hospital death in trauma patients surviving their injuries. We assessed the prevalence, incidence and risk factors for deep venous thrombosis (DVT) and pulmonary embolism (PE) in critically ill trauma patients, in the setting of a mature and early mechanical and pharmacological thromboprophylaxis protocol. Methods: This was a prospective observational study on a cohort of patients from a surgical intensive care unit of a university level 1 trauma centre. We enrolled consecutive primary trauma patients expected to be in intensive care for ≥48 h. Thromboprophylaxis was protocol driven. DVT screening was performed by duplex ultrasound of upper and lower extremities within the first 48 h, between 5 and 7 days and then weekly until discharge. We recorded VTE risk factors at baseline and on each examination day. Independent risk factors were analysed using a multivariate logistic regression. Results: In 153 patients with a mean Injury Severity Score of 23 ± 12, the prevalence of VTE was 30.7%, 95 CI [23.7-38.8] (29.4% DVT and 4.6% PE). The incidence was 18%, 95 CI [14-24] patients-week. The median time of apparition of DVT was 6 days [1; 4]. The global protocol compliance was 77.8% with a median time of introduction of the pharmacological prophylaxis of 1 day [1; 2]. We identified four independent risk factors for VTE: central venous catheter (OR 4.39, 95 CI [1.1-29]), medullar injury (OR 5.59, 95 CI [1.7-12.9]), initial systolic arterial pressure <80 mmHg (OR 3.64, 95 CI [1.3-10.8]), and pelvic fracture (OR 3.04, 95 CI [1.2-7.9]). Conclusion: Despite a rigorous, protocol-driven thromboprophylaxis, critically ill trauma patients showed a high incidence of VTE. Further research is needed to tailor pharmacological prophylaxis and balance the risks and benefits. [ABSTRACT FROM AUTHOR]