Epidemiological data based on phenotypic and molecular characterization of meticillin-resistant Staphylococcus aureus (MRSA) in sub-Saharan Africa are limited. This investigation studied 61 MRSA isolates obtained from 13 health-care institutions in KwaZulu-Natal (KZN) province, South Africa, from March 2001 to August 2003. More than 80 % of the isolates were resistant to at least four classes of antibiotics and six isolates were resistant to the aminoglycoside, macrolide-lincosamide and tetracycline groups of antibiotics, heavy metals and nucleic acid-binding compounds. PFGE of SmaI-digested genomic DNA revealed seven types, designated A-G. Type A was the main pulsotype (62.3 %) and was identified in 11 of the 13 health-care institutions, suggesting that it represented a major clone in health-care institutions in KZN province. Analysis of representative members of the three major pulsotypes by spa, multilocus sequence typing and SCCmec typing revealed the types t064-ST1173-SCCmec IV and t064-ST1338-SCCmec IV (PFGE type A, single-locus and double-locus variants of ST8), t037-ST239-SCCmec III (PFGE type F) and t045-ST5-SCCmec III (PFGE type G). The combination of various typing methods provided useful information on the geographical dissemination of MRSA clones in health-care institutions in KZN province. The observation of major clones circulating in health-care facilities in KZN province indicates that adequate infection control measures are urgently needed.