The preferred product characteristics for a Group A Streptococcus (GAS) vaccine, as outlined by the World Health Organization, recommend effective protection against pharyngitis as a relevant and feasible goal for early phase clinical development. The non-human primate (NHP) model of GAS pharyngitis has been used to investigate vaccine immunogenicity and efficacy. However, vaccines currently in preclinical development have yet to demonstrate a reduction in NHP pharyngeal colonisation following GAS challenge. In this study, we employed the NHP pharyngitis model to investigate the efficacy of the preclinical GAS vaccine Combo#5 formulated with the experimental adjuvant SMQ. SMQ is a squalene-in-water emulsion containing the saponin QS21 and the synthetic toll-like receptor 4 ligand 3D(6-acyl)-PHAD®, which elicits a more balanced Th1/Th2-type immune response compared with the clinically approved vaccine adjuvant alum (aluminium hydroxide). Vaccination of NHPs with Combo#5-SMQ resulted in reduced GAS colonisation compared with negative controls. These findings suggest that the Combo#5-SMQ vaccine formulation protects against pharyngeal colonisation and highlights the feasibility of developing a GAS vaccine that blocks colonisation and subsequent disease burden in humans.