A numerical model is presented for a two-stage seawater reverse osmosis (SWRO) desalination unit with spiral-wound modules. The model, which is based on the mass and momentum transport equations, takes into consideration the longitudinal variation of the velocity, the pressure, and the salt concentration in the membrane modules. This model was calibrated with the field data of a 600 m³/day SWRO unit of the desalination plant of Porto Santo Island (Portugal) and was used to optimize the module configuration and the operating conditions of a medium-sized SWRO with spiral-wound modules. For a typical reverse osmosis (RO) plant with a capacity of 1000 m³/day, with a single stage and four membrane modules (FilmTec SW30HR-380) per pressure vessel, operating at a feed pressure of 6.0 MPa and with an inlet feed velocity of 0.12 m/s, the water recovery rate is 33%, the energy consumption is 4.28 kWh/m³, and the specific water cost is 81.4 eurocent/m³. The water cost can be reduced to 66.7 eurocent/m³, for a two-stage SWRO unit operating at a 56.7% water recovery rate, with seven membrane modules per pressure vessel, operating at transmembrane pressures of 7.2 and 8.0 MPa and inlet feed velocities of 0.23 and 0.20 m/s, in the first and second stages, respectively.