Abstract:Background: Shigellosis and salmonellosis are still global health problems, especially, in developing countries where poor sanitation, lack of clean water supply and proper sewage disposal system exist. The emergence of increased antimicrobial resistance of Shigella and Salmonella species are global challenges, particularly in developing countries like Ethiopia where increased misuse of antimicrobial agents by human beings occur. Objectives: To determine the prevalence and antimicrobial susceptibility patterns of Shigella and Salmonella isolates from patients with diarrhea attending the health institutions in Gondar town, Northwest Ethiopia. Materials and Methods: Health institutional based cross sectional study was carried out on diarrheic patients attending Gondar town health institutions, February 29, 2014 to May 20, 2014. Systematic random sampling technique was used and stool samples were collected from 372 study subjects. Samples were cultured onto MacConkey and Salmonella-Shigella agars and drug susceptibility patterns of the isolates were determined following standard bacteriological method. Data were coded and entered for statistical analysis using SPSS version 20. Data were presented using tables and chi-square. Result: Of the total of 372 stool cultures, 17(4.57%) Shigella spp. and 4(1.08%) Salmonella spp. were isolated. Most commonly isolated strains of Shigella were S. flexneri 11(64.7%) followed by S. dysenteriae 3(17.65%), S. boydii 2(11.77%) and S. sonnei 1(5.88%). Shigella isolates presented high resistance rate to ampicilin (94.1%), amoxicillin (88.2), tetracycline (88.2%) and Salmonella species were highly resistance to tetracycline (100%), amoxicillin (100%), and ampicillin (75%). However, all isolates of Shigella and Salmonella were 100% susceptible to ciprofloxacin and norfloxacin. Conclusion and recommendation: This study revealed that isolates of Shigella and Salmonella showed high rate of drug resistance to the commonly used antibiotics. However, all the isolates were susceptible to ciprofloxacin, and norfloxacin. Therefore, ciprofloxacin and norfloxacin can be used as drugs of choice for the treatment of Shigellosis and Salmonellosis.