The Sao Francisco River is the fourth largest river in Latin America, and particularly important since it crosses the Brazilian semi-arid region. During the 1960s-90s, a series of dams for hydropower were built in cascade, changing drastically the flow regime. To evaluate the influence of changes in the flow on hydrodynamic processes and saline intrusion in the estuary, a three-dimensional hydrodynamic model was applied to the system. The model was calibrated and validated from hydrodynamic data collected in the estuary. The simulated scenarios of river discharges were Q(min), Q(10), Q(80) and Q(max) (corresponding to 600, 5000, 1200, and 12,000 m(3)center dot s(-1), respectively), determined from historical river discharge observations. There was an increase in the mixing and a decrease in the river contribution after the installation of dams. The average salinity in the estuarine domain ranged from 0.7 g center dot kg(-1) for intermediate pre-dam discharge to 15.6 g center dot kg(-1) in the lowest discharges after the dam installations. The results of the simulations were used to establish an exponential relationship between fluvial discharge and saline intrusion, which can be used by management agencies to optimize the water quality in catchments for human consumption.