Abstract: To address the increasing incidence of resistant strains of Salmonella typhi and Salmonella paratyphi, this study was carried out determine the efficacy of different antibiotics against these isolates and to ascertain the existence of multi-drug resistant strains, specifically in the Rawalpindi/Islamabad area. The antibiogram pattern of a total of 22 Salmonella strains, 14 Salmonellatyphi and 8 Salmonellaparatyphi A was determined using the disc diffusion method. The Salmonella isolates were identified through microscopy and biochemical test procedures and were confirmed up to species level by serotyping using the slide agglutination procedure. A total of 22 Salmonella isolates were subjected to antimicrobial sensitivity tests. Of these, 14 (63.6%) were serologically identified as Salmonella typhi and 8 (36.4%) as Salmonella paratyphi A. Out of the 14 Salmonella typhi strains, all of them were found to be sensitive to Amikacin, Ceftraxone, Ciprofloxacin, Enoxacin and Ofloxacin, 11 (78.5%) were also sensitive to Cefazolin/Cefradine, Ceftazidime, Cefotaxime and Gentamicin, while 7 (50%) of the strains were sensitive to Chloramphenicol. Ten strains of the Salmonella typhi strains were determined to be resistant to Ampicillin and Co-trimoxazole, 9 (64.2%) resistant to Tetracycline and 6 (42.8%) resistant to Chloramphenicol. Ten strains were resistant to a combination of Ampicillin plus Co-trimoxazole, 9 (71.42%) resistant to Ampicillin plus Tetracycline and Ampicillin plus Chloramphenicol and 6 (42.8%) of the strains were resistant to Co-trimoxazole plus Tetracycline combination. Seven (87.5%) strains of Salmonellaparatyphi A were sensitive to Ofloxacin and Ceftazidime, while 6 (75%) were determined to be sensitive to Cefotaxime, Enoxacin and Gentamicin. Five (62.5%) of the isolates were found to be resistant to Co-trimoxazole and 4 (50%) resistant to Ampicillin, Cefazolin/Cephradine and Tetracycline. Four (50%) of the Salmonella paratyphi A isolates showed resistivity to a combination of Co-trimoxazole plus Ampicillin, Co-trimoxazole plus Tetracycline and Co-trimoxazole and Cefazolin. With the alarming increase in multi-drug resistant Salmonella typhi and paratyphi A to conventional antibiotics, typhoid fever must be treated very cautiously and newer antibiotics must only be used when they are indicated so as to prevent the further development of microbial resistance against them.