This was a retrospective study in an urban hospital in Kathmandu, Nepal to determine the changing burden of salmonella septicaemia, the proportion of Salmonella paratyphi A, and the emergence of drug-resistant organisms. The participants were outpatients and inpatients over the period 1993-2003, and the main outcome measures were blood culture isolates and antibiotic sensitivity testing. The results showed that of 82467 blood cultures performed, a bacterium was isolated from 12252. Salmonella accounted for 9124 (74.5%) of the positive blood cultures: 6447 (70.7%) were Salmonella enterica serotype Typhi (S. typhi) and 2677 (29.3%) were Paratyphi A (S. paratyphi A). In comparing the period 1997-2000 to the period 2001-2003, we found that, as a proportion of total blood cultures taken, salmonella septicaemia more than doubled, from 6.2 to 13.6% (P<0.001). From the first half of the study (1993-1998) to the second half (1999-2003), S. paratyphi A as a proportion of all salmonella isolates rose from 23 to 34% (P<0.001), which paralleled its increased resistance to ciprofloxacin. Despite the introduction of new antibiotics, enteric fever continues to grow as a cause for hospital presentation in Nepal. Salmonella paratyphi A contributes an increasingly large proportion of cases, and ciprofloxacin resistance is also emerging more rapidly in S. paratyphi A.