Livestock-associated methicillin-resistant Staphylococcus aureus sequence type (ST) 398 (LA- MRSA ST398) is a genetic lineage for which pigs are regarded as the main reservoir. An increasing prevalence of LA-MRSA ST398 has been reported in areas with high livestock density throughout Europe. In this study, we have investigated the drivers contributing to the introduction and spread of LA-MRSA ST398 along the pig farming system in Southern Italy. Whole-genome sequencing (WGS) of LA-MRSA ST398 isolates collected in 2018 from pigs (n=53) and employees (n=14) from 10 farms in the Calabria region were comparatively analysed with previously published WGS data from Italian ST398 isolates (n=45), an international ST398 reference collection (n=89) and isolates from Danish pigs farms (n=283), which are the main suppliers of pigs imported to Italy. Single-nucleotide polymorphisms (SNP) were used to infer isolates relatedness and, together with data from animal trading, factors contributing to LA-MRSA ST398 dissemination were identified. The analyses support the existence of two concurrent pathways for the spread of LA-MRSA ST398 in Southern Italy: i) multiple introductions of LA-MRSA ST398 through the import of colonized pigs from other European countries including Denmark and France and; ii) the spread of distinct clones dependent on local trading of pigs between farms. Phylogenetically related Italian and Danish LA-MRSA ST398 isolates shared extensive similarities including carriage of antimicrobial resistance genes. Our findings highlight the potential risk of transboundary transmission of antimicrobial-resistant bacterial clones with a high zoonotic potential when importing pigs from countries with high LA-MRSA prevalence. [ABSTRACT FROM AUTHOR]