Escherichia coli O157 is a major cause of gastrointestinal illness in humans, and consumption of contaminated food and water is one of the main transmission routes. Because cattle are the primary reservoirs of E. coli O157, vaccines for cattle have been developed but are rarely used owing to licensing issues and other factors. Matthews et al. used veterinary, human surveillance and molecular data to evaluate cross-species transmission dynamics and show that only rare super-shedding events (which involve high densities of the pathogen in excreted cattle faeces) are a serious threat to humans. Because the available vaccines reduce high-density shedding, the authors estimate that they could reduce human cases by nearly 85%, which is a huge improvement on the predicted 50% efficacy previously reported in vaccine trials that did not account for cross-species transmission dynamics.