Currently, two different formulations of Ty21a live oral typhoid vaccine are commercialized. The enteric-coated capsule formulation was licensed based on results of three years of follow-up of a randomized, placebo-controlled, double-blind field trial in Area Occidente, Santiago, Chile, which demonstrated that three doses of this formulation, given on an every other day immunization schedule, conferred the best protection among several options evaluated. Subsequently, a liquid formulation (lyophilized vaccine organisms reconstituted with buffer and water into a vaccine cocktail) was commercialized after it was shown to provide superior protection than enteric-coated capsules over three years of follow-up in a randomized, placebo-controlled field trial in Area Sur Oriente and Area Norte, Santiago. Surveillance in the Area Occidente trial was continued for four additional years (i.e., total seven years of follow-up) and in the Area Sur Oriente/Area Norte trial for two additional years (i.e., a total of five years of follow-up). These additional surveillance data, which were analyzed to ascertain the longevity of protection conferred by these formulations of Ty21a, revealed that three doses of Ty21a in enteric-coated capsules (every other day schedule) conferred 67% protection over three years and 62% protection over seven years of follow-up, whereas three doses of liquid formulation (every other day schedule) elicited 77% protection over three years and 78% over five years of follow-up. Based on its excellent clinical acceptability, ease of oral administration, proven practicality in school-based mass immunization, and long-term efficacy enduring at least seven years, it is proposed that school-based immunization with Ty21a be utilized as a control measure in areas where the incidence of typhoid fever is high and Salmonella typhi are antibiotic-resistant.