•Understand key components necessary for the implementation of a large ACP pragmatic trial.•Understand how to effectively achieve multi-disciplinary stakeholder engagement across multiple sites. Pragmatic trials that implement scalable advance care planning (ACP) interventions in real-world setting are needed. To determine system-level changes needed to implement three scalable ACP interventions: (1) advance directive (AD) alone vs. (2) AD + PREPAREforYourCare website vs. (3) AD + PREPARE + lay navigator for a large cluster-randomized pragmatic trial across three University of California (UC) health systems. The trial includes patients with serious illness from primary care clinics at UC Los Angeles, UC San Francisco, and UC Irvine. Interventions are automatically sent through the electronic health record (EHR, Epic) patient portal and mail. We convened a multi-disciplinary stakeholder advisory board including state/national leaders and, from each site, health system/Population Health leaders, Epic coders, clinicians, patients/caregivers, analysts, and payers. We obtained input from stakeholders and monitored secular trends to determine the key components required to launch this large pragmatic trial. Required key components included: (1) obtaining several administrative, privacy, Epic/patient portal approvals at each site; (2) standardizing local ACP documentation practices and providing education; (3) developing a validated SI algorithm; (4) developing site-specific EPIC code, based on local site structure, to identify patients prior to clinic appointments to receive the intervention while maintaining intervention fidelity; (5) obtaining privacy approvals for mail vendors; (6) obtaining buy-in from over 100 stakeholders to standardize ACP messaging; (7) monitoring ongoing secular trends (e.g., local Epic updates and changing Population Health priorities); and (8) requiring constrained randomization to ensure age and prior AD completion were equal among arms. We have randomized 50 clinics across the three sites, obtained all needed permissions, finalized Epic builds, and launched the trial. The trial will include approximately 7,000 patients. Implementing a large pragmatic trial, with automated, EHR-based cohort identification and intervention delivery, requires a high level of multi-disciplinary stakeholder engagement, standardization, and coordination between sites.