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Credible measures of disease incidence are necessary to guide typhoid fever control efforts. In Egypt, incidence estimates have been derived from hospital-based syndromic surveillance, which may not represent the population with typhoid fever. To determine the population-based incidence of typhoid fever in Fayoum Governorate (pop. 2,240,000), we established laboratory-based surveillance at five tiers of health care. Incidence estimates were adjusted for sampling and test sensitivity. Of 1,815 patients evaluated, cultures yielded 90 (5%) Salmonella Typhi isolates. The estimated incidence of typhoid fever was 59/100,000 persons/year. We estimate 71% of typhoid fever patients are managed by primary care providers. Multidrug-resistant (MDR) Salmonella Typhi (resistant to chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) was isolated from 26 (29%) patients. Population-based surveillance indicates moderate typhoid fever incidence in Fayoum, and a concerning prevalence of MDR typhoid. The majority of patients are evaluated at the primary care level and would not have been detected by hospital-based surveillance.