Fluoroquinolone-resistant Salmonella enterica subspecies enterica serotype Typhi are being increasingly reported from the Asian subcontinent. This has been hypothesised to be due to a double mutation in the gyrA gene. A total of 113 S. Typhi strains isolated during 1987–2006 in a tertiary-level hospital of North India were monitored for their antibiotic susceptibility by the disk diffusion and minimum inhibitory concentration (MIC) methods. The study period was arbitrarily divided into four equal parts, each comprising 5 years. The antibiotics tested showed an extremely wide range of MICs during all four periods except for ceftriaxone, which showed no resistance during the study period. However, a gradual increase in the MIC of this drug was observed, i.e. 0.047mg/L, 0.098mg/L, 0.211mg/L and 0.3652mg/L during the four study periods. Ninety-one percent of the strains isolated in the final study period were observed to have MIC levels ≥0.125mg/L to ciprofloxacin. Furthermore, gyrA restriction analysis showed no mutation at the two reported sites of the gene, suggesting that the double mutation theory in the development of ciprofloxacin resistance may not be the only mechanism responsible for fluoroquinolone resistance.