Health systems are rapidly adjusting and adapting processes to successfully respond to the COVID-19 pandemic. The University of Pennsylvania Health System developed the I-READI (integration, root cause analysis, evidence review, adaptation, dissemination, and implementation) conceptual framework to assist hospitals in preparing for and responding to patient safety challenges during times of crisis, such as the COVID-19 pandemic. The I-READI approach can streamline communication, enrich collaboration, and coordinate rapid change through the use of daily safety huddles, root cause analysis, and technology (e.g., ICU telemedicine and real-time ICU dashboards).