Availability of safe drinking water in the face of arsenic contamination of groundwater has become a global concern, and India is no exception to this alarming problem. Buxar district in the state of Bihar, India, has four blocks affected by arsenic contamination. Groundwater system of the area consists of multiple aquifers, with an arsenic-infested shallow aquifer system and an arsenic-safe deeper aquifer system, separated by a discontinuous clay layer of variable thickness. In response to the increasing demand of potable water, there is a recent trend of either constructing new wells that tap the deeper aquifer or deepening of the existing tube wells. However, unregulated exploitation of the deeper aquifer poses a significant risk, as it can disrupt the hydrodynamics of the entire groundwater system, leading to increased threats of cross-contamination of the deeper arsenic-safe aquifer from the overlying arsenic-contaminated aquifer. In the present study, modelling of the piezometric head of the deeper confined aquifers through distance drawdown analysis using the Theis non-equilibrium equation has been carried out. Findings indicate that the hydraulic head of the deeper aquifer rests at higher level than the water level of the shallow aquifer, thereby acting as a natural flow-pattern defence against the movement of contamination from the shallow aquifer to the deeper aquifer. To address this concern and understand the hydrodynamic balance within the aquifer system, an aquifer response modelling based on Theis non-equilibrium equation has been attempted. This model employs field-determined aquifer parameters to determine the optimal pumping discharge and spacing between wells constructed in the deeper arsenic safe aquifer. The objective is to devise a strategy for keeping the deeper arsenic-safe aquifers protected from any threats of cross-contamination from the overlying arsenic-contaminated aquifer. The results of the study suggest that water supply schemes in the arsenic-affected areas should be designed with a maximum discharge of 50 m3/h. Additionally, a minimum spacing of 2 km between two adjacent high discharge community water supply wells is recommended. The approach presented in the study can be used to determine the safe discharge and optimal spacing criteria between high discharge community water supply wells for pumping the arsenic safe confined aquifers in similar hydrogeological settings. Implementation of the suggested measures is crucial to ensure safe and clean drinking water for present and future generations in the arsenic contaminated areas.