Enteric fever due to Salmonella enterica is a major health problem, and fluoroquinolones such as ciprofloxacin are mostly the antibiotic of choice for the treatment. Resistant to ciprofloxacin has been noticed to increase that due to emergence of new mutations in the bacterial DNA. This study was conducted to explore the fluoroquinolone resistance and molecular characterization of reduced quinolone susceptibility in S. typhi and S.paratyphi A in Kuwait. Methods: A total of 136 clinical isolates of S.typhi and 40 of S. paratyphi A were collected over 5 years. The antimicrobial susceptibility was studied by various methods. DNA sequencing of gyrA, gyrB, parC and parE genes were performed in 31 isolates. Results demonstrated that a substantial difference in MIC range between the two serotypes with the most common MIC for S. typhi being 0.25 mg /L and for S. paratyphiA being 1 mg/L. The proportion of nalidixic acid resistant (NAR) strains increased gradually over the years. These strains had a significantly higher range of MIC of ciprofloxacin (0.023 mg/L ¡V 1.0 mg/L) as compared to the nalidixic acid sensitive (NAS) strains (0.0016 mg/L ¡V 0.125 mg/L). DNA sequencing of gyrA gene showed the presence of three different point mutations: Ser83toPhe in 17 strains, Ser83 to LEU in 3 strains and Asp 87toAsn in 6 strains. No mutations in the other genes were found. Conclusions: It is very important to keep searching for new mutations and continuously monitoring drug-resistance in different parts of the world to efficiently manage cases with enteric fever.