ABSTRACT Background: Staphylococcus epidermidis produces various types of extracellular protein toxins including staphylococcal enterotoxins that act as superantigens, and can provide conditions to attack host cells. The goal of the current study was to determine antibiotic resistance patterns, and detection of prevalent enterotoxin genes in (MRSE) strains containing the ACME-arcA gene in Isfahan. Methods: This survey was done, on a total of 150 staphylococcal isolates acquired from different nosocomial infections. (MRSE) strains isolated by the PCR procedure. The antimicrobial patterns of (MRSE) isolates were determined by the disk diffusion procedure. Finally, enterotoxin genes in (MRSE) strains containing the ACME-arcA gene were detected by using the PCR system.  , Results:  , Out of 150 clinical infections, 100 Staphylococcus epidermidis strains were isolated. Among 100 Staphylococcus epidermidis strains, 65 (65%) isolates were (MRSE). Of these, 33 isolates (50. 7%) had both mecA, and ACME-arcA genes. The antimicrobial patterns of (MRSE) isolates in this study showed that the (MRSE) isolates exhibited the highest rates of resistance to erythromycin (81. 5%), and clindamycin (64. 6%), while they showed the lowest resistance to rifampicin (7. 6%), and linezolid (1. 5%). Moreover, the frequency of enterotoxin genes sea, seb, sec, sed, see, seg, seh, and sei was reported 60. 6%, 63. 6%, 66. 6%, 15. 1%, 6%, 72. 7%, 0%, and 75. 7% respectively, in the isolates containing the mecA, and ACME-arcA genes. Conclusion: The variety of enterotoxin genes types, and resistance index among ACME-arcA encoding (MRSE) are causes for a public health concern, so rapid and accurate reporting of the presence of enterotoxin genes from hospital infections is essential.