Objective.To investigate an outbreak of New Delhi metallo-β-lactamase (NDM)–producing carbapenem-resistant Enterobacteriaceae (CRE) and determine interventions to interrupt transmission.Design, Setting, and Patients.Epidemiologic investigation of an outbreak of NDM-producing CRE among patients at a Colorado acute care hospital.Methods.Case patients had NDM-producing CRE isolated from clinical or rectal surveillance cultures (SCs) collected during the period January 1, 2012, through October 20, 2012. Case patients were identified through microbiology records and 6 rounds of SCs in hospital units where they had resided. CRE isolates were tested by real-time polymerase chain reaction for blaNDM. Medical records were reviewed for epidemiologic links; relatedness of isolates was evaluated by pulsed-field gel electrophoresis (PFGE) and whole genome sequencing (WGS). Infection control (IC) was assessed through staff interviews and direct observations.Results.Two patients were initially identified with NDM-producing CRE during July–August 2012. A third case patient, admitted in May, was identified through microbiology records review. SC identified 5 additional case patients. Patients had resided in 11 different units before identification. All isolates were highly related by PFGE. WGS suggested 3 clusters of CRE. Combining WGS with epidemiology identified 4 units as likely transmission sites. NDM-producing CRE positivity in certain patients was not explained by direct epidemiologic overlap, which suggests that undetected colonized patients were involved in transmission.Conclusions.A 4-month outbreak of NDM-producing CRE occurred at a single hospital, highlighting the risk for spread of these organisms. Combined WGS and epidemiologic data suggested transmission primarily occurred on 4 units. Timely SC, combined with targeted IC measures, were likely responsible for controlling transmission.