Objectives We evaluated the susceptibility to fusidic acid, mupirocin and retapamulin of Staphylococcus aureus isolated from nasal and wound swabs. Methods The susceptibility to the three agents of S. aureus isolated from general patients in the south of The Netherlands with a skin or soft tissue infection was determined between January 2007 and December 2008. Fusidic acid-resistant isolates were tested for the presence of fusidic acid-resistant genes and compared with the epidemic European fusidic acid-resistant impetigo clone (EEFIC). Results Fusidic acid resistance was found in 23% of the nasal and 35% of the wound isolates, the majority (∼90%) being fusB positive. Most of the isolates belonged to spa type t171 and were isolated from younger patients. One isolate was retapamulin resistant (MIC 8 mg/L) and two were mupirocin resistant. Conclusions The EEFIC clone was relatively highly prevalent among the isolated S. aureus . The usefulness of fusidic acid as first-line agent for the treatment of impetigo is questionable. As mupirocin is used in The Netherlands for eradication of methicillin-resistant S. aureus , it is not an alternative; retapamulin might be useful, but further in vivo studies are warranted.