The objective of this study was to analyze the antimicrobial effect of nisin against MRSA (Methicillin-Resistant Staphylococcus aureus) and MSSA (Methicillin-Sensitive Staphylococcus aureus), and at the same time examine the possibility of the bacteria to develope nisin resistance. The antimicrobial susceptibility of the strains was tested using the agar diffusion and/or microdilution methods. To select nisin-resistant strains, bacteria were grown consecutively at sublethal concentrations of the bacteriocin. Nisin showed bactericidal activity against most of the tested strains. MRSA required higher doses of bacteriocin compared to MSSA both for inhibition and cell death. However, transfers in the presence of nisin could completely eliminate nisin activity with an increase in minimal inhibitory concentration value of up to 250 times. Nisin-resistance could be maintained in MRSA and MSSA even in the absence of the bacteriocin. Nisin resistance affected antibiotic susceptibility of both MRSA and MSSA to mainly Cefoxitin, Oxacillin, and Erythromycin. These results indicate that nisin-resistance is a complex trait among MSSA and MRSA and must be elucidated before the therapeutic recommendation of nisin to treat infections caused by these bacterial species.