Background: The frequent treatment failures with empirical therapy observed in some hospitalized typhoid fever patients in the last decade is of great concerned to both public and private physicians owing to the wide spread and circulation of antibiotic resistant strains of S. typhiMethods: This study assessed the trends in antibiotic resistance in 235 Salmonella typhi stains isolated by standard procedures from blood and/stool samples of hospitalized patients from 1997 to 2003. All the isolates were subjected to antimicrobial susceptibility testing using the following antibiotics: chloramphenicol, Ampicillin, cotrimoxazole, tetracycline, nalidixic acid, ciprofloxacin and ofloxacin. Susceptibility and resistance were determined by standard methods.Results: From 1997 through 2003, 188 (80%) of 235 isolates were multiple drug resistant (MDR), chloramphenicol being the most resisted antibiotic (83.0%) followed by Ampicillin (81.7%). Only one strain was resistant to both ciprofloxacin and ofloxacin. Also the prevalence of chloramphenicol resistant isolates increased gradually from 72.4% in 1997 to 89.2% in 2003. Similar trends were recorded for other four antibiotics tested, even for single drug resistance S. typhi isolates. Our study confirmed increased in circulation of MDR-S. typhi isolates over relatively short period.Conclusion: We hereby suggest for a while the immediate stoppage of prescription of chloramphenicol and other first line antibiotics used in the treatment of typhoid fever in Nigeria. The use of more effective drugs such as ofloxacin and ciprofloxacin would go a long way in stemming the prevalence of persons with chronic infections as well as reducing the widespread of MDR-S. typhi strains in our environment, but our fear is that resistance is likely to develop unless these valuable drugs are used prudentl