Disclaimer In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose Inadequate hospital antidote inventory is a widely documented international issue due to high medication costs, lack of emphasis on antidote importance, variable international standards, hospital size, and drug availability. A large health system underwent process and policy implementation for antidote stocking, availability tracking, and administration strategies to ensure appropriate inventory and improve patient safety. Summary Process and policy implementation occurred over a 12-month period across the health system’s 11 acute care hospitals with emergency department services. Opportunities for optimization were identified following data capture surrounding institution-specific antidote inventory and usage across the health system. Specifically, minimum par levels at each institution were determined from 2018 expert recommendations for both the central pharmacy and automated dispensing machines within the emergency department. These quantities ensured the availability of an antidote within a specific timeframe contingent on the acquisition acuity for at least one 100-kg patient. Entries for order sets, order statements, and smart pump drug libraries were modified or formulated to facilitate standardized practices and minimize safety errors before a system-wide electronic health record transition. Conclusion It is prudent for all institutions, independent or within a health system, to identify areas of improvement for antidote inventory and management. Implementation of a similar process for antidote stocking, sharing, and delivery at other institutions is feasible and necessary to mitigate issues with drug acquisition and timely administration.