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In response to the 2014-2016 West Africa Ebola virus disease (EVD) outbreak, a US congressional appropriation provided funds to the US Centers for Disease Control and Prevention (CDC) to support global health security capacity building in 17 partner countries, including Guinea. The 2014 funding enabled CDC to provide more than 300 deployments of personnel to Guinea during the Ebola response, establish a country office, and fund 11 implementing partners through cooperative agreements to support global health security engagement efforts in 4 core technical areas: workforce development, surveillance systems, laboratory systems, and emergency management. This article reflects on almost 4 years of collaboration between CDC and its implementing partners in Guinea during the Ebola outbreak response and the recovery period. We highlight examples of collaborative synergies between cooperative agreement partners and local Guinean partners and discuss the impact of these collaborations in strengthening the above 4 core capacities. Finally, we identify the key elements of the successful collaborations, including communication and information sharing as a core cooperative agreement activity, a flexible funding mechanism, and willingness to adapt to local needs. We hope these observations can serve as guidance for future endeavors seeking to establish strong and effective partnerships between government and nongovernment organizations providing technical and operational assistance.