Objective: The genetic surroundings of blaCTX-M-15 in Escherichia coli recovered from faeces of travellers returning to the UK from overseas were compared with those among established UK strains to provide further insights into the spread of bla(CTX-M-15) in the UK. Methods: From August 2006 to January 2008, 1031 faecal specimens were collected at the North West London NHS Trust from general practice patients with a clinical history of diarrhoea following recent international travel. Cefuroxime-resistant E. coli were isolated on cystine-lactose-electrolyte deficient agar and those that produced extended-spectrum beta-lactamases (ESBLs) were identified by double disc synergy test (DDST). The molecular environments surrounding bla(CTX-M-15) were investigated by PCR, DNA sequencing, gene cloning and northern blotting. Results: 182/1031 (18%) E. coli isolated from returning travellers gave a positive DDST, and were confirmed by PCR to produce CTX-M ESBLs; 174 (96%) had blaCTX-M-15, including 21 belonging to clone ST131. Among these 174 isolates, the environment upstream of blaCTX-M-15 consisted of either: (i) an intact ISEcp1 (n=108); (ii) various lengths of truncated ISEcp1 (n=58); or (iii) a 24 bp remnant of ISEcp1 (n=8). Two different promoters were found to transcribe bla(CTX-M-15), resulting in different levels of cephalosporin resistance. Conclusion: E. coli with CTX-M-15 ESBL from returning travellers harboured previously seen UK bla(CTX-M-15) genetic environments (intact or 24 bp remnant of ISEcp1) as well as bla(CTX-M-15) genetic environments previously unseen in the UK (various lengths of truncated ISEcp1), which suggest overseas acquisition and highlight the difficulty of control in a time of population mobility and travel.