For many years, coagulase-negative staphylococci (CoNS) have been considered non-pathogenic bacteria. However, recently, CoNS are becoming more common bacteriological factors isolated from cases of chronic rhinosinusitis in humans. Moreover, most of them represent the multidrug-resistant or/and methicillin-resistant profile, which significantly increases the therapeutic difficulties. The aim of the study was to characterize profile of resistant coagulase-negative staphylococci isolated from cases of chronic rhinosinusitis in patients treated in a Medical Center in Warsaw in 2015–2016. The study material was derived from patients with diagnosed chronic rhinosinusitis treated at the MML Medical Center in Warsaw. The material was obtained intraoperatively from maxillary, frontal, and ethmoid sinuses. In total, 1,044 strains were isolated from the studied material. Coagulase-negative staphylococci were predominant, with the largest share of Staphylococcus epidermidis. Isolated CoNS were mainly resistant to macrolide, lincosamide, and tetracycline. Among the S. epidermidis strains, we also showed 35.6% of MDR and 34.7% of methicillin-resistant strains. The same values for other non-epidermidis species were 31.5% and 18.5%, respectively and the percentage of strains with MAR >0.2 was greater in S. epidermidis (32.6%) than S. non-epidermidis (23.9%). Although the percentage of strains resistant to tigecycline, glycopeptides, rifampicin and oxazolidinones was very small (2.3%, 1.9%, 1.4% and 0.7% respectively), single strains were reported in both groups. The study has shown a high proportion of MDR and methicillin-resistant CoNS strains, which indicates a large share of drug-resistant microorganisms in the process of persistence of chronic rhinosinusitis; therefore, isolation of this group of microorganisms from clinical cases using aseptic techniques should not be neglected.