BACKGROUND: The eastern provinces of the Democratic Republic of the Congo have been identified as endemic areas for cholera transmission, and despite continuous control efforts, they continue to experience regular cholera outbreaks that occasionally spread to the rest of the country. In a region where access to improved water sources is particularly poor, the question of which improvements in water access should be prioritized to address cholera transmission remains unresolved. This study aimed at investigating the temporal association between water supply interruptions and Cholera Treatment Centre (CTC) admissions in a medium-sized town. METHODS AND FINDINGS: Time-series patterns of daily incidence of suspected cholera cases admitted to the Cholera Treatment Centre in Uvira in South Kivu Province between 2009 and 2014 were examined in relation to the daily variations in volume of water supplied by the town water treatment plant. Quasi-poisson regression and distributed lag nonlinear models up to 12 d were used, adjusting for daily precipitation rates, day of the week, and seasonal variations. A total of 5,745 patients over 5 y of age with acute watery diarrhoea symptoms were admitted to the CTC over the study period of 1,946 d. Following a day without tap water supply, the suspected cholera incidence rate increased on average by 155% over the next 12 d, corresponding to a rate ratio of 2.55 (95% CI: 1.54-4.24), compared to the incidence experienced after a day with optimal production (defined as the 95th percentile-4,794 m3). Suspected cholera cases attributable to a suboptimal tap water supply reached 23.2% of total admissions (95% CI 11.4%-33.2%). Although generally reporting less admissions to the CTC, neighbourhoods with a higher consumption of tap water were more affected by water supply interruptions, with a rate ratio of 3.71 (95% CI: 1.91-7.20) and an attributable fraction of cases of 31.4% (95% CI: 17.3%-42.5%). The analysis did not suggest any association between levels of residual chlorine in the water fed to the distribution network and suspected cholera incidence. Laboratory confirmation of cholera was not available for this analysis. CONCLUSIONS: A clear association is observed between reduced availability of tap water and increased incidence of suspected cholera in the entire town of Uvira in Eastern Democratic Republic of the Congo. Even though access to piped water supplies is low in Uvira, improving the reliability of tap water supply may substantially reduce the incidence of suspected cholera, in particular in neighbourhoods having a higher access to tap water. These results argue in favour of water supply investments that focus on the delivery of a reliable and sustainable water supply, and not only on point-of-use water quality improvements, as is often seen during cholera outbreaks.