In 30% of carriers, Staphylococcus aureus colonization affects exclusively the pharynx and occurs independently from its presence in the nares. This additional reservoir has implications for S. aureus transmission, infection, and decolonization. Host factors promoting colonization of the throat, however, are unknown.We determined pharyngeal and persistent nasal carriage of S. aureus, ABO histo-blood group and ABH secretor status phenotypes in 227 individuals.Compared to group A/non-secretors, group O/non-secretor individuals were at increased risk of carrying S. aureus in their throat (OR 6.50, 95% confidence interval 1.28-33.03, P = 0.02) and group O/secretor individuals were protected (OR 0.24, 0.07-0.77, P = 0.02). Both associations became moderately stronger after adjusting for persistent S. aureus nasal carriage, which was found to be a risk factor for pharyngeal colonization in the univariable analysis (OR 2.41, 1.35-4.33, p = 0.003). Most simultaneous carriers (72%) had identical S. aureus genotypes in their nose and throat.These findings are consistent with in vitro studies that proposed a role of histo-blood group antigens as ligands for S. aureus and support their contribution to the observed population variation in nasopharyngeal S. aureus colonization. Based on their tissue specific expression histo-blood group antigens appear to modulate individual S. aureus colonization patterns.