It has previously been shown that passage of Vibrio cholerae through the human intestine imparts a transient hyperinfectious phenotype that may contribute to the epidemic spread of cholera. The mechanism underlying this human-passaged hyperinfectivity is incompletely understood, in part due to inherent difficulties in recovering and studying organisms that are freshly passed in human stool. Here, we demonstrate that passage of V. cholerae through the infant mouse intestine leads to an equivalent degree of hyperinfectivity as passage through the human host. We have used this infant mouse model of host-passaged hyperinfectivity to characterize the timing and the anatomic location of the competitive advantage of mouse-passaged V. cholerae as well as the contribution of three type IV pili to the phenotype.