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From the initial task of getting "50 deployers within 30 days" into the field to support the 2014-2016 Ebola virus disease (Ebola) epidemic response in West Africa to maintaining well over 200 staff per day in the most affected countries (Guinea, Liberia, and Sierra Leone) during the peak of the response, ensuring the safe and effective deployment of international responders was an unprecedented accomplishment by CDC. Response experiences shared by CDC deployed staff returning from West Africa were quickly incorporated into lessons learned and resulted in new activities to better protect the health, safety, security, and resiliency of responding personnel. Enhanced screening of personnel to better match skill sets and experience with deployment needs was developed as a staffing strategy. The mandatory predeployment briefings were periodically updated with these lessons to ensure that staff were aware of what to expect before, during, and after their deployments. Medical clearance, security awareness, and resiliency programs became a standard part of both predeployment and postdeployment activities. Response experience also led to the identification and provision of more appropriate equipment for the environment. Supporting the social and emotional needs of deployed staff and their families also became an agency focus for care and communication. These enhancements set a precedent as a new standard for future CDC responses, regardless of size or complexity.The activities summarized in this report would not have been possible without collaboration with many U.S and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html).