The bacterium Enterotoxigenic Escherichia coli (E. coli) is a major cause of post-weaning scours in weaned pigs, most frequently causing disease shortly after weaning. Currently no licensed vaccines are available and treatment options are limited, sometimes expensive and marginally effective. We sought an inexpensive and effective preventive measure easily applied to prevent this post-weaning disease in pigs. We hypothesized that an experimental live E. coli vaccine under development in our laboratory may have value as a probiotic for pigs. To test that hypothesis, we fed the vaccine in either of three forms to five-day-old pigs, which should be even more susceptible to E. coli than weaned pigs. Twenty-four hours after piglets were given the vaccine strains, they were challenge-inoculated with highly virulent enterotoxigenic E. coli. The experiment was terminated 24 hours after the challenge and the condition of the pigs was assessed. We found that pigs receiving the complete vaccine were highly protected from disease. They did not develop scours or exhibit other signs of illness. Further, upon postmortem examination, we found that their intestines were largely spared infection by the pathogen. Such as not the case with pigs not given the vaccine strain. They became very ill and their intestines were highly infected. In further studies, we found that the vaccine strain needed to posses the key traits at enabled it to colonize the intestines to be effective. Further, it had to be able to grow rapidly in the intestines and had to possess similar traits to the pathogen to be effective. It appears that the vaccine strain acts as a probiotic by arriving in the intestines before the pathogen and there colonizing the tissues, competitively excluding the pathogen which then finds no place to colonize. We conclude that this approach to a probiotic would provide a convenient and highly protective approach to preventing post-weaning scours during the first days after weaning. Other studies in our laboratory indicate, that piglets do develop immunity from the vaccine strain, which terns the short-term probiotic protection into long-term immunity. Thus, pigs would be perminantly protected from E. coli when this vaccine strain is utilized.