Abstract Background Vaccine recommendations in the United States (US) are made using the Evidence to Recommendation framework, which incorporates values and preferences of the target population. Vaccines for Clostridioides difficile infection (CDI) are in development, but data on preferences to inform potential recommendations are lacking. This study assessed willingness to receive a CDI vaccine and how selected vaccine attributes affect choice. Methods An online survey including a discrete choice experiment (DCE) was conducted with a commercial survey panel October – December 2021 among US adults aged ≥ 50 years. Important vaccine attributes were identified through interviews and literature. Included attributes were vaccine effectiveness (VE), duration of protection, impact on severity of breakthrough infections, dosing schedule, injection site reactions, systemic side effects, and out-of-pocket (OOP) cost (see Figure for levels). Respondents chose among 3 alternatives in a series of 11 choice tasks after reviewing information on CDI. Each choice included 2 hypothetical vaccine profiles and no-vaccine. Preference weights for all attribute levels were estimated via hierarchical Bayesian modelling; attribute relative importance (RI) was based on the difference between least and most preferred levels (the sum of RI across attributes was scaled to equal 100%). Stratified analyses by age, race, gender, and medical conditions were conducted to explore whether preferences varied by these characteristics. Results The sample (N=1,216) was primarily white (91%), female (71%), and retired (54%); vaccination was chosen in 58% of the choice tasks. RI values showed OOP had the most impact on preferences (56%), followed by VE (18%), impact on breakthrough infections (10%), injection site pain (6%), side effects (4%), duration of protection (4%), and dosing schedule (2%), and varied little across subgroups. Attribute-level preference weights for the total sample are depicted in the Figure. Figure.Preference Weights for Clostridioides difficile Vaccine Attributes Values are means. Vertical distance between preference weights indicates strength of preferences for changes within an attribute. Conclusion Survey respondents were receptive to vaccination against CDI, especially when OOP costs were low. The impact of severity of breakthrough infections on preferences highlight the importance of considering effectiveness against severe outcomes alongside overall vaccine effectiveness. Disclosures Jeffrey T. Vietri, PhD, Pfizer Inc: Stocks/Bonds Martine C. Maculaitis, PhD, Cerner Enviza: Employee of Cerner Enviza, which received funding from Pfizer to conduct and report on the study. Joseph C. Cappelleri, PhD, Pfizer Inc.: Stocks/Bonds Holly Yu, MSPH, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Mary M. Moran, MD, Pfizer Inc.: Stocks/Bonds Kathleen Beusterien, MPH, Pfizer: Employee of Cerner Enviza, which consults for Pfizer.