Background: Diarrhoea and acute gastroenteritis are among the leading causes of illnessesrnand deaths in infants and children throughout the world, especially in developing countries.rnGlobally, Salmonella and Shigella remain the major contributors to acute enteric infectionsrnand diarrhoea. Emergence and spread of antimicrobial resistance to newer and more potentrnagents used in treatment have been described for Salmonella and Shigella species. rnObjectives: To isolate and determine the antimicrobial susceptibility pattern of Salmonellarnand Shigella species from children with acute diarrhoea in Mekelle Hospital and SemenrnHealth Center. rnMaterials and Methods: A cross sectional study was conducted among 260 children withrnacute diarrhoea in Mekelle, from November 2011 to March 2012. rnResults: Out of the 260 study participants 145 (55.8%) were males and 115 (44.2%) werernfemales. Majority of the patients (44.2%) were children under five years of age. A total ofrn120 enteropathogens were isolated. The frequency of isolation was 19 (7.3%), 18 (6.9%) andrn83 (31.9%) for Salmonella species, Shigella species and intestinal parasites respectively.rnMost of the Shigella isolates were resistant to ampicillin (88.9%), Tetracycline (77.8),rncotrimoxazole (55.6%) and chloramphenicol (55.6%). Among the Salmonella isolatesrnhighest resistance was observed to ampicillin (89.5%), Tetracycline (89.5%),rnchloramphenicol (78.9%) and cotrimoxazole (57.9%). Multi-drug resistance was noted in 19rn(100%) and 16 (88.9%) of Salmonella and Shigella species respectively. rnConclusion and recommendation: Shigella and Salmonella are still challenging pathogensrnin children < 5 years of age. High antibiotic resistance was observed among both isolates tornampicillin, tetracycline, chloramphenicol and cotrimoxazole. Ciprofloxacin, norfloxacin andrnceftriaxone were effective for all isolates. To reduce the incidence of these enteropathogens,rnimproving personal and food hygiene has to be strengthened. The establishment of antibioticrnpolicy and treatment guideline are recommended based on the susceptibility profile.