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• Fecal Rotarix vaccine virus shedding and HBGAphenotype frequency were investigated. • Virus shedding was higher (23.6%) after the first dose than the second dose (4.7%). • Most of vaccine virus-shedding infants were secretor HBGA positive while none of the non-fecal vaccine virus shedding infants were secretor HBGA positive. Most of the virus-shedders were secretor+ compared to none of the non-virus shedders. • Low vaccine virus shedding was significantly associated with non-secretor phenotype. Histo-blood group antigens are recognized by rotaviruses in a P- genotype dependent manner and their frequency in a population can influence fecal virus shedding. This study investigated the rate of fecal shedding of Rotarix vaccine and its association with HBGA phenotype distribution in South Africa. Stool and saliva specimens were collected from 150 infants attending immunization on the day of both first and second doses and 7 days later. Virus shedding was detected by real-time qPCR while HBGA phenotypes in saliva were determined by enzyme linked immunosorbent assay. Vaccine virus shedding was higher (23.6%) after the first dose than the second dose (4.7%). About 77% of virus-shedding infants were secretors (OR = 129; 95% CI, 6.088 – 2733), compared with none of non-virus shedding infants. Non-secretor status was significantly associated with low vaccine virus shedding while the likelihood of shedding was significantly higher in secretors. [ABSTRACT FROM AUTHOR]