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The purpose of this article was to describe a 2.5-year interventional program designed to control the dissemination after a large hospital outbreak of vancomycin-resistant enterococci (VRE) in a tertiary-care university hospital. A VRE working group was designated to work specifically on controlling VRE intrahospital dissemination after the detection of the first VRE infection at in our hospital in June 2007. The intervention consisted in the interruption of new admissions during a period of 15 days and closure of the index case unit, microbiological surveillance of rectal swabs for VRE, cohorting patients and staff, immediate application of contact precautions, and continuous education. From July 2007 to December 2009, 8,692 rectal swabs were cultured for VRE and 321 (3.7%) were positive. An expressive reduction of the detection of new positive rectal swabs cultures was seen during the year 2009 (1.5%) when compared to 2008 (4.2%) and 2007 (7.2%) (p < 0.005). The annual ratio of VRE per 1,000 admissions reduced from 20.3 in 2007 to 10.07 and 3.82 in 2008 and 2009, respectively (p < 0.001). The continuous microbiologic surveillance for VRE and strict and prompt contact precautions for VRE patients were the fundamental aids in the control of VRE.