INTRODUCTION: The sanitary and epidemiological reliability (SER) of a centralized drinking water supply system (CDWSS) is one of the determining factors of the quality of drinking water, and it is assessed by a special methodology developed by Erisman Federal Scientific Center for Hygiene. AIM: To conduct a comprehensive hygienic assessment of SER considering microbiological parameters of drinking water quality. MATERIALS AND METHODS: The study was conducted jointly with the Center for Hygiene and Epidemiology of the Ryazan region (RR) in six district centers of the RR supplied with water from different aquifers. Water samples were taken according to the standard method of Methodological Guidelines (MUK) 4.2.1018-01. Microbiological parameters of drinking water quality were determined in the selected water samples in accordance with the Sanitary Norms and Regulations (SanPiN) 1.2.3685-21. Statistical analysis was performed using Microsoft Excel 2019 and IBM SPSS Statistics 19. RESULTS: The recorded levels of generalized complex parameter SER of CDWSS were as follows: Skopin, 1.6 points (the most unfavorable situation); Mikhailov, 1.3 points; Ryazhsk, 1.1 points; Kasimov, 0.4 points; and Korablino and Sasovo, 0.3 points each (the least unfavorable situation). In Skopin, Ryazhsk, and Mikhailov, a strong correlation was found between the increased content of the microbiological parameters and the incidence of dysentery and acute intestinal infections of viral etiology in the adolescent population. CONCLUSION: The lowest levels of SER of the CDWSS were recorded in Skopin, Mikhailov, and Ryazhsk. A direct correlation of high strength was found between the exceedance of the permissible values of the microbiological parameters of drinking water and the incidence of dysentery and intestinal infections of viral etiology among adolescents in these towns.