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Large-scale public health emergencies require a sophisticated, coordinated response involving multiple entities to protect health and minimize suffering. However, the rarity of such emergencies presents a barrier to gathering observational data about the effectiveness of the public health response before such events occur. For this reason, public health practitioners increasingly have relied on simulated emergencies, known as “exercises” as proxies to test their emergency capabilities. However, the formal evaluation of performance in these exercises, historically has been inconsistent, and there is little research to describe how data acquired from simulated emergencies actually support conclusions about the quality of the public health emergency response system. Over the past six years, we have designed and evaluated more than seventy public health emergency exercises, collaborating with public health agencies, hospitals and others to test a wide variety of systems and their capabilities. Using the data and experience that we gathered, we have developed a conceptual framework that describes the essential elements necessary to consider when applying performance measurement science to public health emergency exercises. We suggest that this framework may assist practitioners and researchers who wish to better measure performance in exercises and to improve public health emergency preparedness.