Background: Staphylococcus aureus is a common cause of healthcare-acquired morbidity and mortalityand increased healthcare resource utilization. A prophylactic vaccine is being developed that may reducethis disease burden.Methods: Volunteers in good general health aged 50–85 (n = 312) and 18–24 (n = 96) years were random-ized to receive a single intramuscular dose of one of three dose levels of a non-adjuvanted, 3-antigen S.aureus vaccine (SA3Ag) or placebo. SA3Ag antigens included capsular polysaccharides 5 and 8 (CP5 andCP8), each conjugated to cross-reactive material 197 (CRM197), and recombinant clumping factor A (ClfA).Safety, tolerability, and immunogenicity were evaluated.Results: At day 29 post-vaccination, robust immune responses were observed in both age cohorts at allthree SA3Ag dose levels. In the primary analysis population, the 50- to 85-year age stratum, geometricmean-fold-rises in competitive Luminex® immunoassay antibody titers from baseline ranged from 29.2to 83.7 (CP5), 14.1 to 31.0 (CP8), and 37.1 to 42.9 (ClfA), all (P