BACKGROUND: During 2022 and 2023, a large upsurge of cases of Group A Streptococcus (GAS) infection has struck many countries worldwide. This large epidemic event was caused by a diminished level of immunity after COVID-19 social restrictions and was fostered mainly by the emm1 genotype of the bacterium. METHODS: We characterized the genomes of the GAS isolates that caused bloodstream infections in the last ten years in a 900-bed hospital in Northern Italy. We obtained short-read genomes, which we used for emm typing and to analyze the antimicrobial resistance and virulence gene content. Moreover, we contextualized the isolates in an epidemiological point of view using both ortholog-based and SNP-based phylogeny. RESULTS: In the last ten years, we registered two upsurges of GAS cases in the study hospital: one in 2023 (in line with the global epidemiological situation), and one in 2016 (local, but observed also in another recent Italian study). The genomic analysis of the bloodstream infection isolates showed the circulation of multiple emm types, of which emm1, emm12, and emm4 characterized the two large epidemic events. Notably, the 2016 peak was mainly fostered by the M1 CONCLUSIONS: Our results further confirm the role of emm1 as the most prevalent genotype worldwide. However, we also unveiled the central role of genotype emm4 in the 2016 epidemic event, described in the study hospital. Finally, our results suggest the presence of multiple locally persistent strains. Among these, we underlined the presence of a multi-drug resistant strain of emm92.