This study concerns the occurrence of arsenic in the groundwater system of the Cimino-Vico volcanic area (central Italy), different parts of which are currently widely used for local drinking water supply and for irrigation. The system shows a complex groundwater circulation, including a continuous basal aquifer, discontinuous perched aquifers, groundwater flows at high altitude, and local interactions with rising thermal fluids. Data on arsenic contents in 250 water samples from springs and wells and in 68 samples from rock outcrops were measured and combined with already existing information. Results highlight that arsenic concentrations of groundwater are influenced by type of aquifer, groundwater flow path, arsenic content of the aquifer rocks, and interaction with fluids rising from depth. Waters circulating in the Vico volcanics, one of the prominent rock units of the area, have high concentrations of arsenic, both for the basal and the perched aquifers. A large fraction of the waters associated with this rock unit have arsenic contents higher than 10 μg/L (82 percent for basal, 40 percent for perched). In contrast, waters circulating in the Cimino volcanics have lower arsenic contents: 30 percent of the basal and 10 percent of the perched aquifers have arsenic concentrations greater than 10 μg/L. Through an integrated approach, including leaching tests to investigate the arsenic behavior concerning the water-rock interaction and a geostatistical modeling of data, it has been possible to identify and tentatively quantify suitable water resources that have arsenic content not exceeding the quality standards for human consumption.