Recent outbreaks of foot-and-mouth disease virus (FMDV) demonstrate that this highly contagious viral infection of cloven hoofed animals continues to be a significant economic problem worldwide. Debate about the most effective way to respond to outbreaks of FMDV in disease free countries continues to center on the use of vaccines. In this report, we present data showing that a commercially available, standard dose vaccine formulation can fully protect cattle against direct challenge with the virus in as little as 7 days with no carrier transmission to naïve animals. Cattle challenged 4 days after vaccination have reduced disease severity, no detectable virus in blood and little virus shedding from nasal secretions. These significant effects at 4 days post vaccination, confirmed in two separate trials, support the value of using currently available vaccines as a first line of defense against foot-and-mouth disease (FMD) outbreaks.