In the Kathmandu Valley of Nepal, locals depend on multiple water sources due to the limited access to safe water, which is a great global concern regarding its impact on human health. This study aimed to compare the infection risk of diarrhoea from multiple water sources with different concentrations of Escherichia coli among water supply areas and evaluate the impact of changing water sources due to the Gorkha earthquake on the infection risk. The concentration of enteropathogenic E. coli was estimated in samples of piped water, jar water, groundwater, and tanker water, which were collected in the Valley. The volume of each water ingestion was determined based on a questionnaire survey and considering drinking and bathing sources. The highest estimated risk was observed for households drinking groundwater from shallow dug wells, followed by tanker water. The estimated risk implied the regional disparity due to various water sources with different quality. After the earthquake, the ratio of households drinking only jar water increased, and the estimated risk decreased. The damage on piped water supply, the decrease of tanker water availability and the decrease of residents' trust in groundwater quality presumably enhanced the consumption of jar water despite its high price.