OBJECTIVE To determine the prevalence of chronic colonization with methicillin-resistant Staphylococcus aureus (MRSA) in patients with cystic fibrosis, describe antibiotic sensitivity of the strains, and compare the patients' clinical characteristics with those of patients infected with methicillin-sensitive S. aureus (MSSA). METHODS Patients with chronic S. aureus colonization were selected from a total of 50 patients with cystic fibrosis. Sputum samples were cultured according to standard microbiological procedures. Patients were considered to have chronic bronchial colonization if the same microorganism was isolated in 3 consecutive sputum samples, separated by an interval of at least 1 month. The following variables were compared between patients with MSSA (17) and MRSA (8): sex, body mass index, presence of pancreatic insufficiency, bacterial colonization, pulmonary function, Brasfield radiological score, Shwachman clinical score, and number of respiratory exacerbations in the previous year. RESULTS The prevalence of infection by MRSA was 16%. All the MRSA strains were sensitive to vancomycin, teicoplanin, and linezolid. Patients with MRSA were older and had a larger number of respiratory exacerbations than patients with MSSA. CONCLUSIONS There is a high percentage of colonization by MRSA in adult cystic fibrosis patients. Although the pathogenic role of this microorganism remains unclear, patients with MRSA had more frequent exacerbations and poorer lung function. Thus, infection control is important and patients should be adequately monitored.