Background: Methicillin-resistant Staphylococcus aureus (MRSA) has increasingly been implicated to be a causal organism of nosocomial infection. This study aimed at detecting PBP2a and PVL gene in Staphylococcus aureus (S. aureus) and MRSA isolated from in-patients and patients' caregivers in a Sokoto Hospital. Methods: This cross-sectional study involved 201 samples comprising 129 swabs from patients with surgical wounds on admission and 72 swabs from their caregivers/relatives. The samples were screened for S. aureus and MRSA using standard cultural methods, and they were further screened for PBP2a protein and PVL gene using a rapid PBP2a kit and polymerase chain reaction techniques respectively. Results:  Findings showed a 21.9% recovery of S. aureus from the samples and a 70.5% prevalence rate of MRSA among the S. aureus isolates. S. aureus and MRSA were more prevalent in the wound swabs. The PBP2a protein was detected in 27.3% of the S. aureus isolated. It was interesting to note that 61.3% of the MRSA isolates lacked the PBP2a which is known to be an integral part of the mecA gene. The PBP2a was mostly detected in the isolates that came from the wound swabs. The PVL gene was detected in 32.3% of the S. aureus isolates and the PVL-positive isolates were all from wound swabs. Conclusions: The significant linkage of S. aureus isolates under study to methicillin resistance and the PVL gene is a call for caution. Therefore, the trends of MRSA in hospital-related infections should be recurrently investigated to avoid indiscriminate spread.