, after notification of Klebsiella pneumoniae (KP) OXA-48;CTX-M-15 in two patients, nosocomial transmission was suspected in a Dutch hospital. Hospital-wide infection control measures and an outbreak investigation were initiated. A total of 72,147 patients were categorised into groups based on risk of OXA-48 colonisation or infection, and 7,527 were screened for Enterobacteriaceae OXA-48 by polymerase chain reaction (PCR). Stored KP isolates (n=408) were retrospectively tested for OXA-48 and CTX-M-1 group extended-spectrum beta-lactamases (ESBL). 285 KP isolates from retrospective and prospective patient screening were genotyped by amplified fragment length polymorphism (AFLP). 41 isolates harbouring different Enterobacteriaceae species were analysed by plasmid multilocus sequence typing (pMLST). No nosocomial transmission of Enterobacteriaceae OXA-48 was detected after 18 July 2011. Enterobacteriaceae OXA-48 were found in 118 patients (KP (n=99), Escherichia coli (n=56), ≥1 Enterobacteriaceae OXA-48 species (n=52)), of whom 21 had clinical infections. 39/41 (95%) of OXA-48 containing plasmids were identical in pMLST. Minimum inhibitory concentrations (MICs) of KP OXA-48 and E. coli OXA-48 for imipenem and meropenem ranged from ≤1 to ≥16 mg/L, and 153/157 (97%) had MIC >0.25 mg/L for ertapenem. AFLP identified a cluster of 203 genetically linked isolates (62 KP OXA-48;CTX-M15 ; 107 KP CTX-M-15 ; 34 KP OXA-48). The 'oldest' KP CTX-M-15 and KP OXA-48 clonal types originated from February 2009 and September 2010, respectively. The last presumed outbreak-related KP OXA-48 was detected in April 2012. Uncontrolled transmission of KP CTX-M-15 evolved into a nosocomial outbreak of KP OXA-48;CTX-M15 with large phenotypical heterogeneity. Although the outbreak was successfully controlled, the contribution of individual containment measures and of the hospital relocating into a new building just before outbreak notification was impossible to quantify.