Abstract: Diagnostic errors are common and frequently extremely serious. Unfortunately, strategies to identify diagnostic standards and best diagnostic practices for a variety of problems are scarce. The focus of the Center to Improve Clinical Diagnosis will be to tackle diagnostic problems using a data and consensus driven approach. The goals of the Center are to (a) assemble a diverse, multidisciplinary team to provide formal input about standards and best practices; (b) to implement a 4-step strategy to develop recommended diagnostic practices; and (c) to sustain the Center by creating a set of policies, methods, a future agenda, and partnerships within and outside our organization. Our Center will be fully integrated into a larger health services research center within University Hospitals Health System. Our general 4-step process to develop recommended practices includes (1) identifying problems which are common, associated with high rates of diagnostic error, and for which guidance is lacking and identify current diagnostic practice (or practices in response to diagnostic interventions) (2) identify outcomes of diagnostic practices; (3) in collaboration with a panel of diagnosticians, review data about practice and outcomes and formulate recommendations; (4) implement recommendations and monitor their impact. We have chosen three problems as demonstration projects based on how common and serious they are and the expertise and experience of our research team: (1) The best approach to identifying and evaluating unintentional weight loss in adults; (2) The best approach to screening for hypertension in African American adolescents using home-BP devices; (3) Improved diagnosis of sepsis in children in community emergency department (ED) settings, and adults in community (ED) and inpatient settings through implementation and most importantly, refinement of electronic sepsis trigger tools. We believe our systematic approach to developing standards and best practices for these and future problems will provide a system for badly needed diagnostic guidance that is useful for patients, clinicians, and health systems.