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Introduction: Simulation-based clinical systems testing (SbCST) may detect latent safety threats (LSTs) before new systems are implemented. Failure Modes and Effects Analysis (FMEA) scoring allows for triage of LSTs. This single-centered QI project aimed to evaluate LSTs through a human factors lens, and prioritize LSTs through SbCST before implementing an EHR. Methods: Simulations were conducted throughout a Children’s Hospital in a tertiary medical center. General pediatrics, critical care, and ED units were tested 8 weeks prior to go-live. Participants included physicians, nurses, pharmacists, and support staff. Simulations covered critical workflows including traumas, rapid-responses, and cardiac arrests. LSTs identified during simulation testing were categorized using a human factors (SEIPS 2.0) framework. Two reviewers independently assigned SEIPS categories to each LST and reached consensus via discussion. Thematic analysis revealed common patterns across LSTs. To stratify risk, an FMEA scoring tool was used to evaluate severity, likelihood of occurrence, and likelihood of detection on a four-point Likert scale, yielding a risk priority number (RPN). Results: Fifty-seven LSTs were identified. Tools and technology comprised the largest category (n=40), followed by task-related concerns (n=34), and organizational factors (n=13). Although people (n=12) and internal environment (n=4) were less frequent primary drivers, they influenced staff experience of system challenges. FMEA RPN scoring ranged from 4-48, with a median and score of 12, indicating moderate risk. Common themes included challenges navigating the EHR interface during critical workflows, as connectivity and documentation were time-intensive and cognitively burdensome in critical settings. Conclusions: Tools, technology, and task-related factors were the primary drivers of LSTs, particularly around system usability, documentation workflows, and resource ordering. SbCST proved valuable in identifying LSTs in critical care settings, revealing gaps in quality and opportunities to optimize care delivery. Broader application of the SEIPS and FMEA methodology across departments and institutions may optimize LST assessment in SbCST initiatives