Rotarix (GlaxoSmithKline) oral rotavirus vaccine is licensed as 2 doses in the first 6 months of life. In settings with high child mortality rates, clinical protection conferred by 2 doses of Rotarix is reduced. We assessed vaccine immune response when an additional dose of Rotarix was given to Australian Aboriginal children 6 to \lt;12 months old.ORVAC is a 2-stage, double-blind, randomized, placebo-controlled trial. Australian Aboriginal children 6 to \lt;12 months old who had received 1 or 2 prior doses of Rotarix rotavirus vaccine were randomized 1:1 to receive an additional dose of Rotarix or matched placebo. The primary immunological end point was seroresponse defined as an anti-rotavirus immunoglobulin A level ≥20 AU/mL, 28–56 days after the additional dose of Rotarix or placebo.Between March 2018 and August 2020, a total of 253 infants were enrolled. Of these, 178 infants (70\ had analyzable serological results after follow-up; 89 were randomized to receive Rotarix, and 89 to receive placebo. The proportion with seroresponse was 85\2\ to \lt;12 months old increased the proportion with a vaccine seroresponse.NCT02941107.