On August 16, 2012, the Colorado Department of Public Health and Environment was notified of two patients at an acute-care hospital in Denver with carbapenem-resistant Enterobacteriaceae (CRE), specifically Klebsiella pneumoniae (CRKP), isolated from respiratory specimens during July-August. Both isolates produced New Delhi metallo-beta-lactamase (NDM). A review of microbiology records identified a third patient with NDM-producing CRKP isolated from a respiratory specimen, admitted in May. Active surveillance cultures in September identified an additional five patients colonized with NDM-producing CRKP. An investigation was launched by the hospital and the Colorado Department of Public Health and Environment to guide infection control measures and limit transmission.