Recent advances in typhoid vaccine, and consideration of support from Gavi, the Vaccine Alliance, raise the possibility that some endemic countries will introduce typhoid vaccine into public immunization programs. This decision, however, is limited by lack of definitive information on disease burden. We propose use of a vaccine probe study approach. This approach would more clearly assess the total burden of typhoid across different syndromic groups and account for lack of access to care, poor diagnostics, incomplete laboratory testing, lack of mortality and intestinal perforation surveillance, and increasing antibiotic resistance. We propose a cluster randomized trial design using a mass immunization campaign among all age groups, with monitoring over a 4-year period of a variety of outcomes. The primary outcome would be the vaccine preventable disease incidence of prolonged fever hospitalization. Sample size calculations suggest that such a study would be feasible over a reasonable set of assumptions.