Interruptive clinical decision support tools, such as OurPractice Advisories (OPAs), play a critical role in guiding nursing practice but can contribute to alert fatigue when overused or poorly targeted. This initiative focused on optimizing interruptive OPAs to improve relevance and reduce unnecessary disruptions. Through a systematic review and update of advisory content, logic, and firing conditions, we achieved a 52% reduction in the total number of interruptive OPAs fired. Additionally, nurse engagement with OPAs improved significantly: the percentage of advisories where nurses took the intended action increased from 12% to 63%, and the percentage resulting in a discrete action in the electronic health record rose from 11% to over 18%. These outcomes demonstrate that targeted refinement of interruptive alerts can simultaneously decrease alert burden and enhance clinical compliance, supporting safer and more efficient nursing workflows.