The aim of this study was to delineate the potential risks and dynamics of the prolonged carriage of resistant E. coli in returned travellers. A sample of 274 previously collected E. coli resistant to ceftriaxone (CRO), ciprofloxacin, gentamicin and/or nalidixic acid recovered from 102 travellers was studied. Travellers were assessed pre-travel then longitudinally (maximum 6 months) with peri-rectal/rectal swabs. Clonality was determined by REP-PCR and the presence of O25b-ST131 was assessed. Comparison was made longitudinally for individuals and between identified co-travellers. The risk of prolonged carriage was lower for CRO than for ciprofloxacin or gentamicin resistance. Repeated isolation of the same phenotype at different time points occurred in 19% of initial CRO-resistant carriers compared with 50% of ciprofloxacin- or gentamicin-resistant carriers. The duration of carriage was also longer for the latter resistance phenotypes (75th quartile 8 vs 62 and 63 days respectively). In multivariate analysis, risks of prolonged carriage included antimicrobial use whilst travelling (3.3, 1.3-8.4) and phylogenetic group B2 (9.3, 3.4-25.6) and D (3.8, 1.6-8.8). Clonality amongst longitudinal isolates from the same participant was demonstrated in 92% of participants who were assessable and most marked amongst CRO-resistant isolates. ST-131 was surprisingly infrequent (3% of participants). Prolonged carriage of ciprofloxacin- and gentamicin-resistant isolates is more frequent and prolonged than CRO resistance after travel. Risks of prolonged carriage indicate a contribution of host and bacterial factors to this carriage. These require further elucidation. The strong clonality identified suggests that carriage of a "phenotype" was mediated by persistence of bacteria/plasmid combinations rather than persistence of the plasmid after horizontal transfer to other bacteria.