Antibiotic resistance of S. epidermidis isolated from biological specimens is a global problem to public health. In this study a total of 256 S. epidermidis isolates (128 clinical isolates and 128 nasal isolates) from Gaza strip, Palestine were investigated. All isolates were tested for its antimicrobial susceptibilities and carriage of the mecAgene. Out of the 256 isolates, 184 (71.9%) were resistant to multiple antibiotics with all displaying increased susceptibility toward rifampicin (100%), doxycycline (98.4%) and vancomycin (98%). Ninety-six isolates (37.5%) were multidrug resistant (MDR) while, 99 isolates (38.7%) were mecApositive. A significant difference was demonstrated between clinical and nasal isolates. Clinical isolates were significantly more resistant for 8/12 tested antibiotics including resistance to cefoxitin (30μg) (p=0.000) and significantly (p=0.000) represents the MDR isolates while nasal isolates were significantly (p=0.000) sensitive for all tested antibiotics. No significant difference between the two groups in carrying mecA. We find that clinical isolates gain an extra-feature that qualify it to cause a disease and methicillin resistance (MR) was not mecA dependent in all MR isolates.