Background: Methicillin-resistant Staphylococcus aureus (MRSA) has arisen as a hospital-acquired pathogen worldwide. Rapid and accurate detection of MRSA is important to prevent its hospital-acquired infections. Objective: make the comparison between various phenotypic approaches for the detection of the mecA gene with PCR based method as a gold standard. Methodology: Our study was carried out in the Clinical Pathology Department, Faculty of Medicine, Menoufia University between January 2019 to July 2019. A total of 100 clinical isolates of S. aureus, which were collected from various clinical specimens, was a subject of this study. Methicillin resistance was determined by cefoxitin disc diffusion and Chromogenic MeReSa media, the results of these approaches were compared with mecA gene-based PCR method. Results: Among 100 isolates of S. aureus, 78 (78%) isolates were positive for the mecA gene by PCR method. Chromogenic media had identified (76) out of (78) as methicillin-resistant Staphylococcus aureus (MRSA) and (21) out of (22) as methicillin-sensitive Staphylococcus aureus (MSSA) with sensitivity 97.4%, specificity 95.4% Cefoxitin disc had identified (77) out of (78) as MRSA and (21) out of (22) as MSSA with sensitivity 98.7%, specificity 95.4%. Conclusion: The chromogenic media method is less sensitive for the detection of MRSA than the cefoxitin disc diffusion method but they have the same specificity. The phenotypic identification of MRSA has high sensitivity and specificity in agreement with PCR. In addition, they are simple, rapid and not expensive so we can use them in the screening of patients and staff members in health care settings in order to decrease the risk of hospital-acquired infections.