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BACKGROUND: Despite the increasing incidence of venous thromboembolism (VTE) in hospitalized children, the risks and benefits of VTE prophylaxis, particularly for those hospitalized after trauma, are unclear. The Pediatric Trauma Society and the Eastern Association for the Surgery of Trauma convened a writing group to develop a practice management guideline on VTE prophylaxis for this cohort of children using the Grading of Recommendations Assessment, Development, and Evaluation framework. METHODS: A systematic review of MEDLINE using PubMed from January 1946 to July 2015 was performed. The search retrieved English-language articles on VTE prophylaxis in children 0 to 21 years old with trauma. Topics of investigation included pharmacologic and mechanical VTE prophylaxis, active radiologic surveillance for VTE, and risk factors for VTE. RESULTS: Forty-eight articles were identified and 14 were included in the development of the guideline. The quality of evidence was low to very low because of the observational study design and risks of bias. CONCLUSIONS: In children hospitalized after trauma who are at low risk of bleeding, we conditionally recommend pharmacologic prophylaxis be considered for children older than 15 years old and in younger postpubertal children with Injury Severity Score (ISS) greater than 25. For prepubertal children, even with ISS greater than 25, we conditionally recommend against routine pharmacologic prophylaxis. Second, in children hospitalized after trauma, we conditionally recommend mechanical prophylaxis be considered for children older than 15 years and in younger postpubertal children with ISS greater than 25 versus no prophylaxis or in addition to pharmacologic prophylaxis. Lastly, in children hospitalized after trauma, we conditionally recommend against active surveillance for VTE with ultrasound compared with routine daily physical examination alone for earlier detection of VTE. The limited pediatric data and paucity of high-quality evidence preclude providing more definitive recommendations and highlight the need for clinical trials of prophylaxis