Only 3 cases of infective endocarditis (IE) due to methicillin-resistant Staphyhlococcus haemolyticus (MRSH) have been reported in English literature. Here we report 4 cases of IE due to MRSH encountered in a single university hospital. Population analysis of the strains was performed to assess the presence of vancomycin/teicoplanin heteroresistant subpopulations. Pulsed-field gel electrophoresis was used for molecular typing of isolates. IE was defined in 3 cases as health care associated, and in 1 case, as community acquired. A causative strain was lost. Two strains were heteroresistant to teicoplanin, and 1 also to vancomycin. Genome macrorestriction profile studies demonstrated that 2 MRSH isolates belonged to clones A and E, possessing a class C1 mecDNA, whereas I clone was sporadic. All patients were treated with vancomycin plus rifampin. Two patients were cured with antibiotic therapy alone, 1 patient needed surgery, and I patient died. Methicillin-resistant multiresistant S. haemolyticus may represent a difficult-to-treat cause of both community and nosocomially acquired IE. (c) 2007 Elsevier Inc. All right reserved.