Little is known about the genetic diversity of Salmonella enterica serovar Typhi ( S . Typhi) circulating in Latin America. It has been observed that typhoid fever is still endemic in this part of the world; however, a lack of standardized blood culture surveillance across Latin American makes estimating the true disease burden problematic. The Colombian National Health Service established a surveillance system for tracking bacterial pathogens, including S . Typhi, in 2006. Here, we characterized 77 representative Colombian S . Typhi isolates collected between 1997 and 2018 using pulse field gel electrophoresis (PFGE; the accepted genotyping method in Latin America) and whole genome sequencing (WGS). We found that the main S . Typhi clades circulating in Colombia were clades 2.5 and 3.5. Notably, the sequenced S . Typhi isolates from Colombia were closely related in a global phylogeny. Consequently, these data suggest that these are endemic clades circulating in Colombia. We found that AMR in S . Typhi in Colombia was uncommon, with a small subset of organisms exhibiting mutations associated with reduced susceptibility to fluoroquinolones. This is the first time that S . Typhi isolated from Colombia have been characterized by WGS, and after comparing these data with those generated using PFGE, we conclude that PFGE is unsuitable for tracking S . Typhi clones and mapping transmission. The genetic diversity of pathogens such as S . Typhi is limited in Latin America and should be targeted for future surveillance studies incorporating WGS.