Although typhoid fever is no longer endemic in most of the developed world, it remains a major infectious disease in less developed regions and imported cases continue to occur in returning travellers, immigrants or migrant workers. We analysed all 692 isolates of Salmonella enterica subspecies enterica serovar Typhi from cases in England, Scotland and Wales that were sent to the Laboratory of Enteric Pathogens at the Health Protection Agency, Centre for Infections, London, UK between 2000 and 2003. The country of acquisition was known for 416 isolates (60%), and the majority of these (70%) came from India or Pakistan. Overall, 24 countries were listed, mainly in Asia and Africa. A total of 48 phage types were detected, 41% of which were Vi-phage type E1. Antimicrobial susceptibility testing revealed that 22% of isolates were multidrug resistant (MDR) (defined as resistance to chloramphenicol, ampicillin and co-trimoxazole) and 39% were quinolone resistant. A significant number of isolates (n = 49) were sensitive to nalidixic acid by disk test but exhibited low-level ciprofloxacin resistance, suggesting a novel mechanism of resistance and reinforcing the need for minimum inhibitory concentration determination. Overall, 13% of isolates were both MDR and likely to show a poor response to a fluoroquinolone. A third-generation cephalosporin (e.g. ceftriaxone) should be considered as empirical therapy in regions of the Indian subcontinent where resistance is now at high levels as well as in patients returning from these areas. This study helps to describe the epidemiology of antimicrobial drug resistance in typhoid fever.