Diarrhoeal disease is a major health problem throughout the world, and is responsible for high morbidity and mortality mainly among children and especially in developing countries like Nepal. This cross-sectional prospective study was designed to determine the incidence of Cholera, Shigellosis and Salmonellosis along with screening of the possible extended spectrum ?-lactamase producer among multi-drug resistant isolates from 268 diarrhoeal patients visiting different hospitals of Kathmandu valley and 5 other districts of Nepal in the period of April 2010 to January 2011. The specimens were processed by standard microbiological methods and confirmed with serology. Bacteria have been found as one of the common causes of diarrhoea and Cholera as one of the major reasons of diarrhoea. This study indicates a continuing need for resistance surveillance and rational use of antimicrobial agents to reduce the multi-drug resistance.