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Methicillin-resistant Staphylococcus aureus (MRSA) colonization has been considered a risk factor for the development of infection, however, there are no studies that have compared the colonizing and infecting strains using whole-genome sequencing (WGS). The aim of this study is to determine the prevalence of and risk factors for MRSA colonization among long-term care facilities (LTCF) residents of Tenerife (Spain), and to analyze the epidemiological relationship between the colonizing and infecting strains using WGS. A point-prevalence study was carried out at 14 LTCFs in Tenerife from October 2020 to May 2021. Nasal swabs were cultured for MRSA. Colonized residents were followed up for two years. A phylogenetic comparison between colonization and infection strains was performed using WGS. A total of 764 residents were included. The prevalence of colonization by MRSA was 28.1% (n = 215), of which 12 (5.6%) subsequently developed infection. A close genetic relationship between colonization and infection isolates was found in three of the four (75%) residents studied. Our study confirms that colonized residents can develop serious MRSA infections from the same nasal colonization strain. Given the high prevalence of MRSA colonization in these centers, it is necessary to implement strategies with preventive measures to avoid the development of infection and the transmission of MRSA. [ABSTRACT FROM AUTHOR]