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Globally, an estimated 11 to 21 million cases of febrile illness and 117,000 to 161,000 deaths are attributed to typhoid fever each year. Typhoid fever is prevalent mainly in low-resource settings with poor water, and inadequate sanitation and hygiene facilities, with South Asia accounting for a large proportion of the burden. Children bear a substantial burden of the disease. Increasing antimicrobial resistance threatens to limit treatment options for typhoid fever. The WHO, in 2018, recommended the use of a new generation vaccine, typhoid conjugate vaccine (TCV), for the control of typhoid fever in endemic regions; however, data from typhoid-endemic settings were lacking. A randomized controlled trial was therefore conducted in Lalitpur, Nepal, to assess the impact of TCV. In this phase III participant-observer-blind randomized controlled trial, children aged 9 months to under-16 years old, were individually randomized (1:1) to either receive the TCV (Typbar-TCV, Bharat Biotech) or a capsular group A meningococcal conjugate vaccine (MenA) as control, and were followed-up for two years. The protective efficacy of TCV against blood culture-confirmed typhoid fever at two years was 79.0% (95% confidence interval (CI): 61.9%, 88.5%; P<0.001). Administration of TCV reduced the incidence of typhoid fever (72 (95% CI: 38,123) cases per 100,000 person-years) compared with the control group (Incidence (MenA group): 342 (95% CI 262, 438) cases per 100,000 person-years). The results of this trial represent one of the first findings confirming that TCV is efficacious in a setting of high endemicity. As a direct result of the findings of this trial and with GAVI support, TCV introduction has been implemented in policy in Nepal. TCV is now routinely administered to children at 15 months of age as part of the national immunization schedule. In this thesis, I describe the design, implementation and results of the trial conducted in Nepal.