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The Cleveland Clinic experience with care paths, including their creation and implementation, challenges overcome during development and testing, and outcomes of selected care path evaluations, is described.Care paths are tools to assist healthcare professionals in practicing evidence-based medicine. The Cleveland Clinic health system has implemented or is developing approximately 100 care paths, including care paths designed to optimize management of sepsis and septic shock and to promote timely use of i.v. tissue plasminogen activator and correct dosing of antithrombotics and statins in patients with stroke. Key steps in successful care path initiatives include (1) identifying key stakeholders, (2) achieving stakeholder consensus on a standardized approach to disease or condition management, (3) cultivating provider awareness of care paths, (4) incorporating care path tools into the electronic health record and workflow processes, and (5) securing the resources to develop, implement, and maintain care paths. Electronic health records facilitate the use of and adherence to care paths. After care path implementation, revisions are typically needed due to unexpected issues not initially identified and to optimize care path features and support resources for clinical practice. Ongoing evaluation is required to determine whether an implemented care path is producing the intended patient and quality performance outcomes.Care paths provide a standardized approach to treatment or prevention of a disease or condition, reducing unnecessary variability and expense while promoting optimal, cost-effective patient care.