Clostridium difficile is the most common cause of healthcare-associated infections (HAIs) in the US, causing at least 450,000 infections and 29,000 associated deaths per year. Current C. difficile infection (CDI) prevention strategies have not decreased CDI. These strategies focus on preventing C. difficile transmission only from patients with symptomatic CDI, and ignore the much more common asymptomatic C. difficile carriers. Asymptomatic C. difficile carriers contaminate the hospital environment, transfer C. difficile spores to healthcare workers hands, and introduce strains associated with subsequent CDI cases. In addition, recent studies suggest at least 30% to 50% of new CDI cases are a result of transmission from asymptomatic C. difficile carriers. However, the potential impact of interventions directed at asymptomatic C. difficile carriers has not been adequately studied. One such strategy to prevent C. difficile transmission among hospitalized patients would be the use of gowns and gloves (contact precautions) for patients asymptomatically colonized with C. difficile. Identifying reductions in C. difficile transmission from asymptomatic carriers with contact precautions would change the paradigm of C. difficile prevention. We hypothesize that patients asymptomatically colonized with C. difficile are important for transmission in the hospital, and use of contact precautions for these patients will lead to decrease in patient-to-patient transmission of C. difficile. The study design is a retrospective analysis of stored specimens that were obtained from a 20 hospital cluster- randomized trial. Aim 1 will assess whether wearing gloves and gowns for all patient contact decreases acquisition of and infection with C. difficile. Aim 2 will assess the relative importance of colonization pressure with C. difficile on C. difficile transmission, and Aim 3 will determine if the NAP-1/027 strain is more transmissible than other strains. This innovative approach will develop the first randomized trial level data to guide C. difficile infection prevention and will inform science on the importance of individuals asymptomatically colonized with NAP-1/027 or other C. difficile strains. This proposal will go beyond the original cluster trial in Aim 1 to assess key questions of colonization pressure, contact precautions and NAP-1/027 on C. difficile transmission.