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ABSTRACT: Objectives: Cystic fibrosis (CF) is a hereditary recessive disease that affects the mucous clearance of the lungs and allows bacteria such as Staphylococcus aureus to settle in the lung and cause infection. This study examined the prevalence of antibiotic resistance of S. aureus in cystic fibrosis infection using a systematic review and meta-analysis. Methods: A comprehensive and systematic search of related articles was conducted through the PubMed, Scopus, and Web of Science databases until March 2022. The weighted pooled resistance rate of antibiotics was analysed with Freeman-Tukey double arcsine transformation in the Stata software version 17.1 using the Metaprop command. Results: In this meta-analysis, 25 studies were used based on criteria to evaluate the pattern of S. aureus resistance in CF. Vancomycin and teicoplanin were the most effective options for treatment of CF patients; the highest level of antibiotic resistance observed was to erythromycin and clindamycin. Conclusion: High levels of resistance to most of the antibiotics studied was observed. The high levels of antibiotic resistance observed are worrisome and indicate the need to monitor antibiotic use.