Background: The Emergency Department (ED) is a medical setting increasingly utilized by opioid users. In January 2016, our health system initiated a take-home naloxone education and distribution program. From July to August 2016, screening was performed in the ED to identify patients for take-home naloxone., Objective: To evaluate the outcomes of routine screening for take-home naloxone in the ED setting and to determine key screening questions. Secondary analysis of Electronic Health Records for discrete elements that could help identify individuals for naloxone., Methods: This is a single-center, retrospective cohort study conducted at two EDs within an academic health system. A screening tool was verbally administered to a convenience sample of ED patients as part of a pilot project to identify patients for overdose education and naloxone. Patient charts were reviewed retrospectively for pre-determined historical elements, medications prescribed, and substance use history. Descriptive and comparative analysis using Fisher two-tailed tests were performed with regard to historical elements, naloxone recommendation and prescription., Results: A total of 182 patients were included. Following screening, 58 (31.9%) were identified as candidates for take-home naloxone. Of those, 36 (62.1%) accepted naloxone recommendation and 19 (32.8%) were prescribed naloxone. Individuals not prescribed naloxone despite recommendation either declined naloxone 22 (37.9%) or were not prescribed naloxone 17 (29.3%). Subanalysis of questions with binary yes/no answers (N = 171) demonstrated significant prediction of both naloxone recommendation (ROC = 0.944) and prescription (ROC = 0.897)., Conclusions: Routine screening for take-home naloxone can help identify patients at-risk for opioid overdose and increase naloxone access in the ED., (Copyright © 2018 Elsevier Inc. All rights reserved.)