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Water scarcity has become a critical problem in many semiarid and arid regions. The single largest water use in such regions is for crop irrigation, which typically relies on groundwater and surface water sources. With increasing stress on these traditional water sources, it is important to consider alternative irrigation sources for areas with limited freshwater resources. One potential irrigation water resource is treated wastewater for agricultural fields located near urban centers. In addition, treated wastewater can contribute an appreciable amount of necessary nutrients for plants. The suitability of reclaimed water for specific applications depends on water quality and usage requirements. The main factors that determine the suitability of recycled water for agricultural irrigation are salinity, heavy metals, and pathogens, which cause adverse effects on human, plants, and soils. In this paper, we develop a regional water reuse decision-support model (RWRM) using the general algebraic modeling system to analyze the cost-effectiveness of alternative treatment trains to generate irrigation water from reclaimed wastewater, with the irrigation water designed to meet crop requirements as well as California’s wastewater reuse regulations (Title 22). Using a cost-minimization framework, least-cost solutions consisting of treatment processes and their intensities (blending ratios) are identified to produce alternative irrigation sources for citrus and turfgrass. Our analysis illustrates the benefits of employing an optimization framework and flexible treatment design to identify cost-effective blending opportunities that may produce high-quality irrigation water for a wide range of end uses.