Clostridium difficile is one of the most important and widespread causes of acute gastroenteritis. Due to the limitations of current therapeutic options there is a need for the development for new treatment methods. Probiotics are an alternative treatment option that have gained prominence in the last few yearsmethod, and the ability of various probiotics to mitigate C. difficile infection was tested. The probiotics Lactobacillus rhamnosus GG and Saccharomyces boulardii demonstrated the greatest mitigative effect, showing signification protection against C. difficile induced death, bioactive toxin and shedding of pathogen within feces in the germ free mouse model. The probiotics also demonstrated protective effects by delaying the onset of C. difficile induced mortality as well in the conventional mouse model. Thus, some probiotics could potentially be used to help mitigate symptoms of C. difficile associated disease.