Objective: Captopril is a long-acting human angiotensin-converting enzyme (ACE) inhibitor that has been used to treat hypertension and heart failure for many years. In this study, it was aimed to determine the antimicrobial activity of L-captopril on Methicillin-Resistant Staphylococcus aureus MRSA and Methicillin-Sensitive Staphylococcus aureus (MSSA) clinical isolates and, demonstrate the combination activity of captopril with ciprofloxacin (CXP) and gentamicin (GEN), which are among antistaphylococcal chemical agents. Method: The minimum inhibitor concentration (MIC) and minimum bactericidal concentration (MBC) were determined using the microdilution technique in 96-well microtiter plates. The activity of L-captopril and CXP or GEN combination against MRSA and MSSA clinical isolates was determined by the micro-broth checkerboard assay method. Results: The captopril MIC value was determined to be 2.5 mg/ml in all bacteria strains tested. The captopril/CXP combination had an indifferent effect in the other strains tested except for one MRSA isolate. The captopril/GEN combination had an antagonistic effect in all strains studied and increased the MIC 2-4 fold. The captopril/GEN combination was found to reduce the bactericidal activity of gentamicin. Conclusions: The study results suggest that exposure to these drugs may lead to multidrug resistance in S. aureus bacteria. Especially in the hypertensive patient group, the induced resistance in any S. aureus infections should be taken into consideration while using captopril and, it should be considered that this antagonism may cause an increase in S. aureus infections.