A vancomycin-resistant Enterococcus (VRE) outbreak occurred at a hematology/oncology (HO) service in a tertiary acute care hospital, 1 January to 30 April 2002. This study was undertaken to identify risk factors, and to establish relations between seasonal factors and this VRE outbreak. Every patient (n = 82) and health care worker (HCW) (n = 31) at the HO unit was screened by rectal swab and stool culture during the VRE outbreak. Environmental surface culture (n = 35) and pulsed-field gel electrophoresis (PFGE) of VRE isolates were preformed. Among a total of 82 patients, 17 had VRE. All VRE isolates were E. faecium, the 6 studied further were Van A with identical PFGE patterns. Cultures of surfaces and HCWs were negative for VRE. Prolonged hospital stay (p = 0.02), male gender (p = 0.02), and care in a 6-bed room (p < 0.01) were risk factors for acquisition of VRE. An association with the VRE outbreak period was found again for long hospital stay, but also for the antibiotic usage pattern, frequent surgery and a high proportion of new inexperienced staff (52% vs 4% before the outbreak (p < 0.01, Fisher's exact test). Sudden personnel turnover in high-risk units should be avoided.