Modern healthcare systems are increasingly organized according to diagnosis-specific clinical pathways and treatment protocols. At the same time, the number of patients with complex problems and needs that do not fit the single-diagnosis approach is rising, contributing to a high prevalence of diagnostic errors. In this article, we focus on the risk of diagnostic errors arising from missed or incomplete diagnosis and assessment of older adult patients’ care needs in the first hours of acute hospitalizations in EDs. This focus is important for improving patient safety, as clinical decisions made in EDs impact patient safety in the subsequent steps of the process, thereby potentially causing new risks to arise. Based on our discussion of clinical decision-making and diagnostic errors in the acute care context, we propose a more comprehensive interdisciplinary approach to improvements in patient safety that integrates organizational and clinical research and examines where, when, how, and why risks to patient safety arise in and across different clinical–organizational contexts.