Arsenic (As) contamination of groundwater drinking sources was investigated in the Mekong Delta, Vietnam in order to assess the occurrence of As in the groundwater, and the magnitude of As exposure of local residents through measurements of As in toenails of residents consuming groundwater as their major drinking water source. Groundwater (n=68) and toenail (n=62) samples were collected in Dong Thap Province, adjacent to the Mekong River, in southern Vietnam. Fifty-three percent (n=36) of the wells tested had As content above the World Health Organization's (WHO) recommended limit of 10 ppb. Samples were divided into Northern (mean As=4.0 ppb) and Southern (329.0 ppb) groups; wells from the Southern group were located closer to the Mekong River. Elevated As contents were associated with depth (<200 m), salinity (low salinity), and redox state (reducing conditions) of the study groundwater. In 79% of the wells, As was primarily composed of the reduced As(III) species. Arsenic content in nails collected from local residents was significantly correlated to As in drinking water (r=0.49, p<0.001), and the relationship improved for pairs in which As in drinking water was higher than 1 ppb (r=0.56, p<0.001). Survey data show that the ratio of As in nail to As in water varied among residents, reflecting differential As bioaccumulation in specific exposed sub-populations. The data show that water filtration and diet, particularly increased consumption of animal protein and dairy, and reduced consumption of seafood, were associated with lower ratios of As in nail to As in water and thus could play important roles in mitigating As exposure in areas where As-rich groundwater is the primary drinking water source.