Background: Diagnosis of pleural effusion (PE) infection and the isolated organismsreported a significant resistance to the commonly used antibiotics, and the choice of appropriate antibiotics for the management should be guided by microbiological results. Objectives: This study aimed to detect the bacterial profile and antibiotics susceptibility pattern of PE isolates and the prevalence of methicillin-resistant Staph. aureus. Methodology: Plural fluid samples from 121 patients with PE infection were collected for microbiological identification and antibiotic sensitivity testing by Vitek 2 system, Staphylococcal aureus isolates were tested for MecA gene by RT-PCR. Results: 47% of PE samples exhibited positive culture, the most encountered organisms were Staph. aureus (24.2%), Klebsiella pneumoniae (16.1%), Staph aureus had the highest sensitivity to Vancomycin and Linezolid (100%) and (40%) of Staph aureus had mecA gene. Conclusion: Bacteria isolated from PE exhibited increasing levels of antibiotic resistance that should be reflected in the choice of empirical antimicrobial treatment.