In post-acute care (PAC) settings, residents face elevated risks of adverse drug reactions and emergency department visits because of polypharmacy. With over 90% of PAC residents nationally taking five or more medications, targeted deprescribing of inappropriate or unnecessary medications emerges as a critical strategy. The project site faces high rates of polypharmacy with a root cause analysis revealing a deficiency in evidence-based practices (EBP) for deprescribing potentially inappropriate or unnecessary medications. To address this issue, a bundled deprescribing intervention was implemented as part of a quality improvement project aimed at reducing polypharmacy rates. This project, conducted at a PAC setting in the midwestern United States, used the RE-AIM Model. Data collection involved tracking prescribing rates before and after the intervention for residents admitted to the practice setting over a 5-month period. A bundled EBP intervention comprising a deprescribing framework, pharmacist collaboration, and the utilization of an EBP guideline, established a systematic process guiding deprescribing efforts for each resident on admission to the PAC setting. Fourty-nine patients received a deprescribing bundle, resulting in a 26.67% reduction in prescribed medications. On average, patients had 5.55 medications deprescribed, with reductions noted across 85 distinct therapeutic drug categories. Nurse practitioners play a pivotal role initiating successful deprescribing interventions within the PAC setting. Using a comprehensive approach, integrating pharmacist collaboration and EBP leads to reductions in prescribing rates among PAC residents. This model demonstrates potential for sustainable improvements in patient outcomes within the PAC environment.