Climate change is impacting water resources in the Mekong Delta of Vietnam. In such context, this paper assesses the potential for wastewater reuse as an adaptation measure to cope with water scarcity in Can Tho City, within the heart of the Mekong Delta. Authors show that wastewater effluent can be used to irrigate at least to 22,719 ha of paddy rice (16% of the rice-cultivated area in the city) at 3 crops per year. The fertilizing properties of the water would eliminate part of the demand for synthetic fertilizers, providing a maximum of 22% of the nitrogen (N) and 14% of the phosphorus (P) requirement for the winter-spring crop. On a yearly basis, recovery of wastewater could reduce the discharge of N by 15-27% and the discharge of P by 8-17%. Such a program would contribute to a decrease in the level of pollution in the local rivers and canal systems, while also reducing the need for expensive tertiary treatment.