Multidrug-resistant (MDR) Staphylococcus aureus has been increasingly isolated from pigs and people in close contact with them, especially livestock-associated methicillin-resistant S. aureus (LA-MRSA). In this cross-sectional study, we investigated S. aureus colonization in pigs and farm workers, their resistance profile, and genetic background to estimate interspecies transmission potential within farms from Rio de Janeiro state, Brazil, between 2014 and 2019. We collected nasal swabs from 230 pigs and 27 workers from 16 and 10 farms, respectively. Five MDR strains were subjected to whole genome sequencing. Fourteen (6.1%) pigs and seven (25.9%) humans were colonized with S. aureus, mostly (64-71%) MDR strains. Resistance to clindamycin, erythromycin, penicillin, and tetracycline was the most common among the pig and human strains investigated. MDR strains shared several resistance genes [blaZ, dfrG, fexA, lsa(E), and tet(M)]. Pig and human strains recovered from the same farm shared the same genetic background and antimicrobial resistance profile. LA-MRSA ST398-SCCmecV-t011 was isolated from pigs in two farms and from a farm worker in one of them, suggesting interspecies transmission. The association between pig management practices and MDR S. aureus colonization might be investigated in additional studies.