Clostridium difficile is the most common cause of bacterial-induced, antibiotic-associated diarrhoea in hospitals among the developed world. Colonisation of the human colon and the establishment of fulminant disease is a complex process that depends on the ingestion of C. difficile spores, which enter the GI tract and germinate in the intestinal mucosa. The resulting vegetative cells cause disease following the production of the major toxins TcdA and TcdB. These toxins are released by pathogenic strains of C. difficile and cause a scope of disease that ranges from mild diarrhoea to more severe conditions such as pseudomembranous colitis and toxic megacolon. Recently, the emergence of strains of increased virulence has driven the need for novel preventive or treatment strategies. Primary treatment for infection includes the administration of vancomycin or metronidazole, however, the continued use of antibiotics increases patient susceptibility to relapse as they prevent re-establishment of the gut microflora. Thus, the development of antibiotic-free therapies is desirable. Bovine colostrum contains a high concentration of immunoglobulins, which can be manipulated to contain high levels of antigen-specific antibodies through immunisation of cows during pregnancy. Cows were vaccinated with either C. difficile spores or toxin and the resulting colostrum-derived antibodies were examined for their ability to prevent or treat disease in a mouse model of infection. Administration of colostrum to mice was shown to be protective against C. difficile disease. Mice that received spore-specific antibodies prior to infection exhibited delayed weight loss and increased survival compared to mice that received colostrum from unvaccinated cows. Mice that received toxin-specific antibodies showed increased weight gain and a high survival rate. Furthermore, when administered post-infection, toxin-specific antibodies were able to halt disease progression. Collectively, these results indicate that C. difficile-specific colostrum may be used as a novel passive immunotherapy strategy for the prevention or treatment of C. difficile infection.