Between 1999 and 2003, meticillin-resistant Staphylococcus aureus (MRSA) isolates recovered from blood cultures in Irish hospitals that participate in the European Antimicrobial Resistance Surveillance System were investigated by epidemiological typing using antibiogram-resistogram (AR) typing, biotyping, and DNA macrorestriction digestion using SmaI followed by pulsed-field gel electrophoresis (PFGE). PFGE patterns were assigned five-digit pulsed-field type (PFT) numbers, and PFTs of apparently related patterns were abbreviated to two-digit PFT groups (PFGs). AR and PFGE typing results were combined to produce AR-PFG types. Representative isolates of each AR-PFG type recovered in 2002 were typed by multilocus sequence typing and staphylococcal cassette chromosome (SCC) mec analysis. Isolates from 1999 and 2000 were also typed by phage typing. The extent to which epidemiological types of MRSA from blood cultures could be extrapolated to the total MRSA population was investigated by comparing results obtained with isolates from the total MRSA population versus those obtained with blood cultures during three study periods. Over the 5 years from 1999 to 2003, 1,580 blood culture isolates from 1,495 patients were analysed. Typeability and discriminatory indices were as follows: AR typing, 1 and 0.97; phage typing, 0.29 and 0.89; PFGE, 0.99 and 0.95; AR-PFG typing, 1 and 0.95. The most frequently occurring AR-PFG types were 06-01, 07-02, 13-00, and 14-00 and were exhibited by 57, 7, 14, and 12% of isolates, respectively. During the study period, the distribution of AR-PFG type changed markedly, with the prevalence of one type (AR-PFG 06-01) increasing by 880%, from 22% (39/181) in 1999 to 80% (343/430) in 2003. Investigation of whether epidemiological types among blood culture isolates of MRSA were representative of the total MRSA population showed that there was no significant difference in most instances. MLST and SCCmec typing showed that AR-PFG types 06-01, 07-02, 13-00, and 14-00 were ST22-MRSA-IV, ST36-MRSA-II, ST8-MRSA-IID, and ST8-MRSA-IIE, respectively.