BACKGROUND: A novel human parechovirus 3 Australian recombinant (HPeV3-AR) strain emerged in 2013 and coincided with biennial outbreaks of sepsis-like illnesses in infants. We evaluated the molecular evolution of the HPeV-AR strain and its association with severe HPeV infections. METHODS: HPeV3-positive samples collected from hospitalized infants aged 5-252 days in two Australian states (2013-2020) and from a community-based birth cohort (2010-2014) were sequenced. Coding regions were used to conduct phylogenetic and evolutionary analyses. A recombinant-specific PCR was designed and utilized to screen all clinical and community HPeV3-positive samples. RESULTS: Complete coding regions of 54 cases were obtained, which showed the HPeV3-AR strain progressively evolving, particularly in the 3' end of the non-structural genes. The HPeV3-AR strain was not detected in the community birth cohort until the initial outbreak in late 2013. High-throughput screening showed most (>75%) hospitalized HPeV3 cases involved the AR strain in the first three clinical outbreaks, with declining prevalence in the 2019-20 season. The AR strain was not statistically associated with increased clinical severity amongst hospitalised infants. DISCUSSION: The HPeV3-AR was the dominant strain during the study period. Increased hospital admissions may have been from a temporary fitness advantage and/or increased virulence.