Background Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant global health threat, particularly within the ESKAPE pathogens. Surveillance in Sub-Saharan Africa, including Gabon, remains limited despite reported high rates of Panton-Valentine leukocidin (PVL)-positive S. aureus and emerging MRSA clones.Methods: A prospective longitudinal study was conducted at two hospitals in Northern (CHRO) and Southeastern (CHUAB) Gabon. Nasal swabs were collected from 200 patients (100 per hospital) upon admission (D0) and serially over 6 days. Environmental swabs were also taken. S. aureus isolates were identified, and MRSA confirmed of mecA gene detection. Characterization included spa typing, SCCmec typing, the lukS/F-PV gene detection, antimicrobial susceptibility testing (EUCAST), and detection of the dfrG trimethoprim resistance gene. Clonal complexes (CC) were inferred.Results: MRSA nasal carriage prevalence was worrying high (60% of S. aureus carriers overall), reaching 70% at CHRO. PVL genes (65% of MRSA isolates) were occurring equally in community-associated (CA, 63%) and hospital-associated (HA, 69%) MRSA. CC5-ST5 (primarily spa t311/t003, SCCmec IV) dominated CA-MRSA (37%) and environmental isolates. Other virulent CA-MRSA clones (CC8, CC80, CC152) were detected. A high proportion of strains were non-typeable by MLST-CC (72% patient, 78% environmental) and SCCmec (37% CA-MRSA), suggesting novel lineages. MRSA exhibited resistance: tetracycline (59%), trimethoprim-sulfamethoxazole (SXT, 31%; 94% mediated by dfrG), ciprofloxacin (26%). No significant resistance difference existed between CA-and HA-MRSA. Environmental contamination was extensive (72% of environmental S. aureus were MRSA), with overlapping clones (CC5-ST5, CC121, spa t653) implicating crosstransmission. Cumulative incidence indicated a 17.1% risk of acquiring new colonization within 6 days of admission. MRSA burden was significantly higher at the northern border hospital (CHRO).Conclusion: This study reveals a critical public health threat in Gabonese hospitals, characterized by virulent (high PVL), resistant MRSA clones circulating actively between patients and the environment. The dominance of CC5-ST5 in CA-MRSA, high rates of non-typeable strains highlight unique epidemiological features.