Introduction: Staphylococcus epidermidis strains are frequently associated with catheter-related infection, acute bacteremia, and hospital-acquired infection. Some isolates produce an extracellular matrix called slime that may make them more resistant to antibiotics. The aim of this study was to determine antimicrobial resistance patterns, the prevalence of slime production, and the distribution of genes (mecA and aap, respectively) associated with these phenotypes in S. epidermidis nasal isolates from health-care personnel. Methodology: A descriptive cross-sectional study was performed on 163 nasal swabs from health-care staff (one swab per subject). S. epidermidis isolates were tested for slime production on congo red agar and antibiotic resistance. PCR-based screening for mecA and aap genes was performed upon the extracted DNA of S. epidermidis isolates. Results: A total of 99 S. epidermidis strains were cultured from 58.9% of the study participants (n = 96). Of these strains, 34 (34.3%) isolates produced slime. A significant relation between slime production and resistance to penicillin 32(94%) , oxacillin 30(88%),, tetracycline 20(59%), erythromycin 27(79%), and clindamycin 26(77%) was found. Respectively, 95.8% and 94.8% of all isolates were PCR-positive for mecA and aap, but only 59.8% of mecA+ strains were oxacillin-resistant and 37.3% of aap+ strains were slime producers. Conclusions: The surveillance of nasal colonization with slime-forming oxacillin-resistant S. epidermidis in health-care workers might be helpful in breaking the epidemiological chain of hospital-acquired infections.