The transmission of meticillin-resistant Staphylococcus aureus (MRSA) between individual patients is difficult to track in institutions where MRSA is endemic. We investigated the transmission of MRSA where ST22-MRSA-IV is endemic on four wards using demographic data, patient and environmental screening, and molecular typing of isolates. A total of 939 patients were screened, 636 within 72 h of admission (on admission) and 303 >72 h after admission, and 1,252 environmental samples were obtained. Isolates were typed by spa, dru and pulsed-field gel electrophoresis (PFGE) typing. A composite dendrogram generated from the three sets of typing data was used to divide isolates into 'dendrogram groups' (DGs). Ten percent of patients (92/939) were MRSA-positive; 7 % (44/636) on admission and 16 % (48/303) >72 h after admission (p = 0.0007). MRSA was recovered from 5 % of environmental specimens (65/1,252). Most isolates from patients (97 %, 85/88) and the environment (97 %, 63/65) exhibited the ST22-MRSA-IV genotype. Four DGs (DG1, DG4, DG16 and DG17) accounted for 58 % of ST22-MRSA-IV isolates from patients. Epidemiological evidence suggested cross-transmission among 44/92 patients (48 %) but molecular typing confirmed probable cross-transmission in only 11 instances (13 %, 11/88), with the majority of cross-transmission (64 %; 7/11) occurring on one ward. In the setting of highly clonal endemic MRSA, the combination of local epidemiology, PFGE, spa and dru typing provided valuable insights into MRSA transmission.