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The Vietnamese Mekong Delta (VMD) is one of the largest rice-growing areas in Vietnam, and exports a huge amount of rice products to destinations around the world. Multi-dike protection systems have been built to prevent flooding, and have supported agricultural intensification since the early 1990s. Semi-dike and full-dike systems have been used to grow double and triple rice, respectively. Only a small number of studies have been conducted to evaluate the water quality in the VMD. This study aimed to analyze the spatiotemporal variation of water quality inside the dike-protected area. Surface water samples were collected in the dry and wet seasons at 35 locations. We used multivariate statistical analyses to examine various water quality parameters. The mean concentrations of COD, NH4+, NO3-, PO43-, EC, and turbidity were significantly higher in water samples inside the full-dike system than in water samples from outside the full-dike systems and inside the semi-dike systems in both seasons. High concentrations of PO43- were detected in most of the primary canals along which residential, tourist areas and local markets were settled. However, NO3- was mainly found to be higher in secondary canals, where chemical fertilizers were used for rice intensification inside the dike system. Water control infrastructures are useful for preventing flood hazards. However, this has an adverse effect on maintaining water quality in the study area.