The aim of this study was to better understand the effectiveness of Integrated Disease Surveillance and Response (IDSR) facility-based surveillance in detecting newly emerging infectious diseases (EIDs) in rural West African settings. A six-month ethnographic study was undertaken in 2012 in the Techiman Municipality of the Brong-Ahafo Region of Ghana, aimed at documenting the trajectories of febrile illness cases of unknown origin occurring within four rural communities. Particular attention was paid to where these trajectories involved the use of formal healthcare facilities and the diagnostic practices that occurred there. Seventy-six participants were enrolled in the study, and 24 complete episodes of illness were documented. While participants routinely used hospital treatment when confronted with enduring or severe illness, the diagnostic process within clinical settings meant that an unusual diagnosis, such as an EID, was unlikely to be considered. Facility-based surveillance is unlikely to be effective in detecting EIDs due to a combination of clinical care practices and the time constraints associated with individual episodes of illness, particularly in the resource-limited settings of rural West Africa, where febrile illness due to malaria is common and specific diagnostic assays are largely unavailable. The success of the ‘One Health' approach to EIDs in West Africa is predicated on characterization of accurately diagnosed disease burdens. To this end, we must address inefficiencies in the dominant approaches to EID surveillance and the weaknesses of health systems in the region generally.