Background. Enteric fever caused by Salmonella Typhi remains a major public health problem in developing countries. Typbar-TCV is a single-dose typhoid Vi polysaccharide-tetanus toxoid conjugate vaccine for persons ≥6 months of age. Methods. Six hundred fifty-four healthy subjects aged 2–45 years enrolled in a double-blind, randomized controlled trial (RCT) received a single dose of Typbar-TCV or comparator "Vi polysaccharide" (Typbar), and 327 healthy subjects aged 6–23 months received a single dose of Typbar-TCV in an open-label trial (OLT); both received single- or multidose presentations from different lots. After 2 years, subsets in each group received a booster dose. The primary objective included analysis of geometric mean titer (GMTs) and 4-fold rise of anti-Vi serum immunoglobulin G (IgG) enzyme-linked immunosorbent assay titers over baseline (seroconversion SCN) 42 days after immunization. Results. Typbar-TCV recipients in the RCT attained higher anti-Vi IgG GMTs 42 days after immunization (SCN, 97%; GMT, 1293 95% confidence interval {CI}, 1153–1449) than recipients of (SCN, 93%; GMT, 411 95% CI, 359–471) (P<.001). Typbar-TCV was highly immunogenic in the OLT (SCN, 98%; GMT, 1937 95% CI, 1785–2103). Two years after vaccination, anti-Vi titers remained higher in Typbar-TCV subjects (GMT, 82 95% CI, 73–92); and exhibited higher avidity (geometric mean avidity index GMAI, 60%) than in Typbar recipients (GMT, 46 95% CI, 40–53; GMAI 46%) in the RCT (P < .001). OLT Typbar-TCV recipients achieved GMT of 48 (95% CI, 42–55) and GMAI of 57%. Typbar-TCV induced multiple IgG subclasses and strong booster responses in all ages. No serious vaccine-attributable adverse events were observed. Conclusions. Single-dose Typbar-TCV is well tolerated and induces robust and long-lasting serum anti-Vi IgG across age groups. Clinical Trials Registration. CTRI/2011/08/001957, CTRI/2014/01/004341.