The World Health Organization’s preferred product characteristics for a vaccine against Streptococcus pyogenes (StrepA) recommends pharyngitis as a relevant and feasible early vaccine development target. The non-human primate (NHP) model of StrepA pharyngitis has been used to investigate vaccine immunogenicity and efficacy, however, vaccines under preclinical development have not yet demonstrated reduced NHP pharyngeal colonization following StrepA challenge. Here, we employ the NHP pharyngitis model to investigate the efficacy of a preclinical StrepA vaccine, Combo#5 formulated with the experimental adjuvant SMQ. SMQ adjuvant is a squalene-in-water emulsion containing the saponin QS21 and 3-O-desacyl-4’-monophosphoryl lipid A which elicits a more balanced balanced Th1/Th2-type immune response compared with Alum. Vaccination of NHPs with Combo#5-SMQ resulted in reduced StrepA colonization compared with negative controls. These findings suggest the feasibility of developing a StrepA vaccine that blocks colonization and subsequent disease burden in humans.