PROJECT SUMMARY At least 37% of patients treated in the emergency department (ED) are discharged without a definitive diagnosis, thus leaving the encounter with diagnostic uncertainty. Transitions of care are high-risk periods for patient safety, especially when patients are discharged with diagnostic uncertainty, and thus are still within the diagnostic process. Effective communication between clinicians and patients is essential to improve the quality of these care transitions. In prior AHRQ-funded research, we developed several tools to support high quality discharge in the setting of diagnostic uncertainty, including a communication checklist, a training program for physicians in uncertainty communication, and a patient-facing 1-page information sheet about being discharged with uncertainty. We now propose to leverage the electronic health record (EHR) to implement a multifaceted strategy to facilitate higher quality discharge transitions for patients discharged from the ED with diagnostic uncertainty. Our Targeted EHR-based Communication about Uncertainty (TECU) strategy will be activated every time an ED clinician enters an uncertain diagnosis for a patient being discharged, and will notify the clinician to counsel the patient about uncertainty while additionally triggering automated 1) insertion and printing of the patient handout, 2) printing of the clinician-facing checklist to guide the discharge conversation, and 3) sending of an inbox message to the primary care provider (PCP). We will conduct a pre- post pilot trial with a hybrid type 1 effectiveness implementation design with the goals of: 1) Testing the preliminary effectiveness of TECU compared to standard of care in reducing patient uncertainty and return ED visits and 2) Evaluating the adoption of TECU and exploring patient and clinician barriers and facilitators to TECU implementation. This work will be led by experienced researchers with expertise in health services research, clinical trials in emergency medicine, patient communication, health literacy, diagnostic uncertainty, informatics, and implementation science. The TECU strategy will be easily disseminated as it will be built in Epic, the world’s leading EHR vendor, and will be available for health systems to implement through the Epic Community Library. This project has potential to significantly impact the quality and safety of care transitions for the one-third of patients leaving the emergency department with diagnostic uncertainty.