Two patients with infectious endocarditis (IE) by Staphylococcus aureus resistant to methicillin, aminoglucosides and rifampicin (SARMAR) acquired in hospital during the course of an epidemic outbreak of this microorganism in the Hospital Clínic i Provincial of Barcelona. Both patients had undergone surgery of the lower limbs. The entrance of the microorganism was the infection of the surgical wound, with bacteriemia, followed by mitral IE after a short time interval (20 days). Despite adequate treatment with vancomycin both patients died. The culture of mitral vegetation was positive for SARMAR in one. Analysis of the chromosomic DNA of all the isolations from the patients was identical and coincided with that of the SARMAR strains isolated in the epidemic outbreak of the hospital. The current situation of IE by SARMAR is reviewed and the therapeutic implications commented upon suggesting that treatment of this entity should simultaneously include the administration of vancomycin and phosphomycin or cotrimoxazole, with surgery being considered if infection persists.