Aims: This study was aimed to design comprehensive risk management based on hazard analysis and critical control points (HACCP) in the Isfahan drinking water system. Materials and Methods: Data obtained from field inspections and through related organizations of Isfahan, Iran. The most important risks and risky events of water quality in all sources of raw water in the study area including the Zayanderoud river, the water treatment plant, and the distribution system were identified and analyzed. Practical measures for the protection, control, and limitation of the risks in different phases, from water supply to consumption point, were presented in the form of seven principles of the HACCP system. Results: It was found that there was a potential of hazards during the treatment process of water because of seasonal changes and discharge of various pollutants. Water contamination could occur in eight identified critical control points (CCP). River water could be contaminated by rural communities on the banks of the river, by natural and sudden accidents, by subversive accidents, by incomplete operation, by lack of proportionate of the current treatment process, and by the high extent of antiquity of the Isfahan water distribution system. Conclusions: In order to provide safe drinking water, it is necessary to implement a modern risk management system such as the HACCP approach. The increasing trend of the Zayandehroud river pollution needs urgent attention. Therefore, the role of the government in developing and mandating the HACCP system in water industries is essential.