Every year, millions of people in the United States are diagnosed with a multi-drug resistant organism (MDRO), increasing costs and mortality rates. The overuse and misuse of antimicrobial therapies contribute to the rise in MDROs which causes antimicrobial resistance (AMR). Antimicrobial Stewardship Programs (ASPs) can help decrease AMR in healthcare settings. The purpose of this project was to develop, implement, and evaluate a nurse-led interdisciplinary ASP within the acute care setting. Bedside nurses completed an online descriptive survey before and after implementing interdisciplinary stewardship rounds. Education on antimicrobial stewardship was provided to the bedside nurses using a web-based educational module, guided script for rounds, and just-in-time training. Shewhart charts were used to determine special and common cause variations related to hospital-onset Clostridium difficile rates, central line-associated bloodstream infections per catheter days, and catheter-associated urinary tract infections per catheter days. Engaging nurses and integrating nursing practice into ASPs led to increased utilization of nurse-driven catheter removal protocols and the rationalization of necessary treatments. The acceptance rates for discontinuing unnecessary antibiotic therapy and removing indwelling urinary catheters were 92% and 85%, respectively. Additionally, bedside nurses gained more knowledge regarding ASPs and their pivotal role in making a difference in AMR. Nurse-led interdisciplinary rounds are an effective strategy to implement and strengthen ASPs in acute care. Connecting the role of the bedside nurse to the difference they can make in AMR reveals that nurses who are educated and trained in antimicrobial stewardship can result in better patient outcomes.