ABSTRACT Surgical site infections are the most common post-operative infections even in hospitals with most modern facilities complications and standard protocols of pre-operative preparation and antibiotic prophylaxis. Staphylococci stay as our natural flora and yet sometimes threaten our life as tenacious pathogens. In addition to their ability to evade our immune system, the multi-drug resistance phenotype makes Staphylococci the most intractable pathogenic bacteria in the history of antibiotic chemotherapy. Staphylococci are among the leading causes of nosocomial infections such as surgical site infections. Increasing resistance to β-lactams and the glycopeptides complicates treatment of infections caused by Stahpylococci. The aim of this study is to investigate the antibiotic resistance profile of Staphylococci isolated from surgical site infection. Staphylococci isolates were identified morphologically, by Gram stain and biochemical tests. Antimicrobial susceptibility testing was done by the Kirby-Bauer standard disk diffusion method. One hundred Staphylococci isolates were recovered from one hundred and ninety samples isolated from surgical site infections. Staphylococcus aureus was the most predominant one. From 100 isolates, Staphylococcus aureus was found in 91 isolate and coagulase-negative Staphylococci (CoNS) in 9 isolates. Staphylococcus aureus isolates were highly resistant to tigecycline, oxacillin, ampicillin and ampicillin-sulbactam antibiotics. They showed intermediate resistance to daptomycin, amikacin, azithromycin, levofloxacin, clindamycin, sulfamethoxazole-trimethoprime, doxycycline and gatifloxacin, while they showed low resistance to vancomycin, linezolid and imipenem. On the other hand, CoNS isolates were highly resistant to doxycycline, oxacillin, ampicillin and ampicillin- sulbactam antibiotics. They showed intermediate resistance to daptomycin, levofloxacin, clindamycin, sulfamethoxazole-trimethoprime, gatifloxacin, vancomycin, tigecycline, linezolid and imipenem, while they showed low resistance to amikacin and complete sensitivity to azithromycin. Eighty four isolates were multi-drug resistant. Percentage of multi-drug resistant Staphylococci isolates were very high. This may be attributed to the misuse of antibiotics. To minimize resistance, strict antimicrobial prescription policy should be applied