This paper presents a new approach to divide large Water Distribution Networks (WDN) into suitable District Metered Areas (DMAs). It uses a hydraulic simulator and two operational models to identify the optimal number of DMAs, their entry points and boundary valves, and the network reinforcement/replacement needs throughout the project plan. The first model divides the WDN into suitable DMAs based on graph theory concepts and some user-defined criteria. The second model uses a simulated annealing algorithm to identify the optimal number and location of entry points and boundary valves, and the pipes reinforcement/replacement, necessary to meet the velocity and pressure requirements. The objective function is the difference between the economic benefits in terms of water loss reduction (arising from the average pressure reduction) and the cost of implementing the DMAs. To illustrate the proposed methodology, the results from a hypothetical case study are presented and discussed.