The aim of this study was to comprehensively characteriseS. aureusfrom the Caribbean Islands of Trinidad and Tobago, and Jamaica. A total of 101S. aureus/argenteusisolates were collected in 2020, mainly from patients with skin and soft tissue infections. They were characterised by DNA microarray allowing the detection of ca. 170 target genes and assignment to clonal complexes (CC)s and strains. In addition, the in vitro production of Panton–Valentine leukocidin (PVL) was examined by an experimental lateral flow assay. Two isolates were identified asS. argenteus, CC2596. The remainingS. aureusisolates were assigned to 21 CCs. The PVL rate among methicillin-susceptibleS. aureus(MSSA) isolates was high (38/101), and 37 of the 38 genotypically positive isolates also yielded positive lateral flow results. The isolate that did not produce PVL was genome-sequenced, and it was shown to have a frameshift mutation inagrC. The high rate of PVL genes can be attributed to the presence of a known local CC8–MSSA clone in Trinidad and Tobago (n = 12) and to CC152–MSSA (n = 15). In contrast to earlier surveys, the USA300 clone was not found, although one MSSA isolate carried the ACME element, probably being amecA-deficient derivative of this strain. Ten isolates, all from Trinidad and Tobago, were identified as MRSA. The pandemic ST239–MRSA–III strain was still common (n = 7), but five isolates showed a composite SCCmecelement not observed elsewhere. Three isolates were sequenced. That showed a group of genes (among others,speG,crzC,andccrA/B-4) to be linked to its SCC element, as previously found in some CC5– and CC8–MRSA, as well as inS. epidermidis. The other three MRSA belonged to CC22, CC72, and CC88, indicating epidemiological connections to Africa and the Middle East.