The optimal operation of water distribution networks under local pipe failures, such as water main breaks, was proposed.Based on a hydraulic analysis and a simulation of water distribution networks, a macroscopic model for a network under a local pipe failure was established by the statistical regression. After the operation objectives under a local pipe failure were determined, the optimal operation model was developed and solved by the genetic algorithm. The program was developed and examined by a city distribution network. The optimal operation altative shows that the electricity cost is saved approximately 11%, the income of the water corporation is increased approximately 5%, and the pressure in the water distribution network is distributed evenly to ensure the network safe operation. Therefore, the proposed method for optimal operation under local pipe failure is feasible and cost-effective.