The reported prevalence of vancomycin-resistant Enterococcus faecium (VRE) in Switzerland for the years 2008–2010 has been low at <5%. At the University Hospital Zurich, 17 cases of VRE were detected between 28 December 2009 and 15 February 2010. Nine cases were diagnosed clinically; eight cases were detected by rectal screening. The centre of the outbreak was the cardiac surgery department. Four patients suffered from VRE-infections; four patients died. In order to investigate and contain the outbreak, the following measures were taken: prevalence surveys using weekly rectal screening, environmental screening; selective enrichment culturing; pulsed field gel electrophoresis (PFGE) for clonal typing and polymerase chain reaction-analysis (PCR) for resistance determinants and virulence factors detection. Contact isolation in single rooms and enhanced surface-disinfection methods were implemented. Ward nurses were assigned as link nurses. Regular teaching was carried out aiming to improve hand disinfection among healthcare workers. PFGE revealed two main pulsotypes each including seven patients. Five minor pulsotypes originated from three additional patients and one sample collected from a keyboard. Two of three patients with minor pulsotypes had been treated abroad. PCR-analysis identified vanB resistance-genotypes with exception of one vanA resistance-genotype. The outbreak was associated with environmental contamination and insufficient compliance with hand-hygiene. Enhanced awareness and infection control measures resulted in termination of the VRE outbreak within eight weeks. The complexity of the outbreak with several clones in parallel suggests a higher baseline prevalence of VRE in Switzerland than previous surveillance data indicate.