Staphylococcus aureus, which is described as a common nosocomial pathogen has acquired an ability to cause a wide range of infections and has been found to be one of major organisms associated with multi-drug resistant and high morbidity and mortality worldwide. The objective of this study was to assess the antibiotic resistance of Staphylococcus aureus strains isolated from clinical specimens in Ouagadougou. Staphylococcus aureus strains were isolated from different clinical specimens collected in four hospitals in Ouagadougou for a period running from April 2018 to March 2019. Classical bacteriological methods were used for isolation and identification of the strains. All strains were subjected to a set of 12 antibiotics to study their antibiogram by using the Kirby-Bauer disk diffusion method. A total of 150 isolates of S. aureus were collected during the study period. S. aureus isolates were mostly from pus specimens (60%) from patients between 20 and 59 years old. Antibiotics resistance testing showed that the proportion of methicillin-resistant Staphylococcus aureus (MRSA) among the isolates was 31.33% (47/150). Most of these MRSA (63.83%) were multidrug-resistant. 71.43% of MRSA isolates exhibited resistance to several antibiotics, while 42.4% of MRSA isolated in outpatient was multidrug-resistant strains. Tetracyclin resistance was very frequent (58.7%), followed by levofloxacin (56.25%), ciprofloxacin (44.12%), kanamycin (36%) and erythromycin (30%). This multidrug-resistance was most frequent in isolates from hospitalized patients. This study has revealed alarming levels of MRSA isolates and high cross-resistance to antibiotics other than those of the free-lactam family in Ouagadougou.