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Background: Alcohol withdrawal syndrome (AWS) in surgical trauma patients is associated with significant morbidity and mortality. Benzodiazepines, commonly used for withdrawal management, pose unique challenges in this population given the high prevalence of head trauma and delirium. Phenobarbital is an antiepileptic drug that offers a viable alternative to benzodiazepines for AWS treatment., Methods: This is a retrospective chart review of patients with active alcohol use disorder who presented to a level 1 trauma center over a 4-year period and required medication-assisted management for AWS. The primary outcome variable examined was the development of AWS and associated complications. Additional outcomes measured included hospital length of stay, mortality, and medication-related adverse events., Results: Of the 85 patients in the study sample, 52 received a fixed-dose benzodiazepine-based protocol and 33 received phenobarbital-based protocol. In the benzodiazepine-based protocol group, 25 patients (48.2%) developed AWD and 38 (73.1%) developed uncomplicated AWS, as compared to 0 patients in the phenobarbital-based protocol (P = 0.0001). There were 10 (19.2%) patients with medication adverse side effects in the benzodiazepine-based protocol group versus 0 patients in the phenobarbital-based protocol group. There were no statically significant differences between the 2 groups as pertains to rates of other AWS-related complications, patient mortality, or length of stay., Conclusion: The use of a phenobarbital-based protocol in trauma patients with underlying active alcohol use disorder resulted in a statistically significant decrease in the incidence of AWD and uncomplicated AWS secondary to AWS when compared to patients treated with a fixed-dose benzodiazepine-based protocol., (Copyright © 2020 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.)