A prevalence survey of methicillin-resistant Staphylococcus aureus (MRSA) was performed in 2010 in 19 long-term care facilities in Luxembourg. Of the 954 participating residents, 69 (7·2%) were colonized by MRSA. Previous history of MRSA [odds ratio (OR) 7·20, 95% confidence interval (CI) 3·19–16·27], quinolone therapy in the previous year (OR 2·27, 95% CI 1·17–4·41) and ⩾24 h care administered per week (OR 4·29, 95% CI 1·18–15·56) were independent risk factors for MRSA colonization. More than 75% of strains were of clonal complex (CC)5, mainly spa-type t003 or sequence type (ST)225 and ST710, which is a rapidly emerging lineage prevalent in central Europe. Five residents were colonized by livestock-associated genotypes belonging to CC398. Previously dominant CC8 strains have recently been replaced by more resistant CC5 strains in Luxembourg.