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This concept depends on the behavior and the uses of the groundwater. The main aim of this study is to propose a scientific basis for sustainable land use planning and groundwater management of the Moulares-Reayef aquifer, located in Southwestern Tunisia. The overexploitation of this aquifer causes the threat of groundwater quality by various sources of pollution. The global vulnerability index was applied in the Moulares-Reayef aquifer. The results show that the most favorable zones to pollutant percolation are situated along the wadis (Tabaddit, Zallaz, Berka,...) which are drained by continuous discharges. The global vulnerability values were correlated with nitrates values for validation. It revealed a significant correlation showing that high values of nitrates occurred in highly vulnerable zones with a value of 0.69 for the Pearson coefficient. The global vulnerability evaluation shows that the aquifer is characterized by high vertical vulnerability and high susceptibility. 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