Background: Enteric fever caused by Salmonella Typhi, gram negative bacilli, is counted as a major public health problem, especially in underdeveloped countries of tropic region. One of the notorious and potentially lethal complications of typhoid fever is small bowel perforation. Chloramphenicol, in 1948 converted this lethal disease to curable one. Efficacy of this drug reduced within 2 years. These strains of salmonella typhi were also found resistant to sulphonamide, tetracycline and streptomycin and are called as multidrug-resistant strains salmonella typhi (MDRST). Due to this resistance amoxycilin, and trimethprim with sulphamethoxazole replaced these drugs. Emergence of MDRST led to the use of quinolones as the first line drug. With the developing resistance to flouroquinolones, 3rd generation cephalosporins such as ceftriaxone and cefotaxime are now increasingly being used in the treatment of typhoid fever. Materials and Methods: This prospective, descriptive study was conducted at surgical ward- III of Liaquat university hospital, Hyderabad from Jan 2007 to Dec 2010. All patients of either sex above the age of 02 years having high-grade fever for more than 1 week associated with features of peritonitis secondary to hollow viscus perforation and later on confirmed through various investigations as cases of perforation of hollow viscus due to typhoid were included in the study. Subject's data was collected for age, sex, mode of presentation, treatment history, & blood culture and sensitivity pattern. Variable studied in this study were age, sex & Sensitivity pattern of Salmonella Typhi in Typhoid small bowel perforation Antibiotics assessed for sensitivity after culture of the organism were: ampicillin, amoxycilin, augmentin, ceftriaxone, cefotaxime, ceftazidime, cefixime, cefipime, cefuroxime, chloramphenicol, amikacin, gentamicin, Ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin, imipenem, meropenem, Piperacillin with Cefbactum and sulphonamide derivative. Results: During the study period of 4 years; a total of 41/187(21.92%) blood culture isolates were identified for salmonella typhi. Mean age of this group of patients was 27.35 years. Amongst them 113(60.42%) were male and 74(39.57%) were female. The antibiotics sensitivity showed that all organisms were sensitive to imipenem and meropenem while sensitivity of the organism to Piperacillin with Sulbactum was 97.56%. 90.24% isolates were sensitive to cefotaxime and ceftazidime while 95.12% & 92.68% to Cefipime & Ceftriaxone respectively. Sensitivity pattern of salmonella typhi to ciprofloxacin, ofloxacin, levofloxacin and moxifloxacin was 80.48%, 73.17%, 82.92% and 85.36% respectively. 41.46% Isolates were resistant to amoxycilin; and 63.41% to Chloramphenicol. Conclusion: This study concludes that there is an increasing resistant trend of salmonella typhi to 2nd line drugs like ciprofloxacin, and 3rd generation cephalosporins. At the same time there is re-emergence of chloramphenicol sensitivity.