Using the response surface methodology (RSM) coupled with computational fluid dynamics, the hydrodynamic and mass transfer have been investigated in a spacer-filled channel. Geometry of an industrial reverse osmosis spiral-wound membrane module has been set to optimize the pressure drop, water permeation flux and the spacer configuration efficacy with respect to the average inlet velocity, the spacer attack angle and the spacer mesh angle. Several tools have been used to implement the response surface methodology: The Latin Hypercube Sampling Design method for design points generation, the Kriging model for interpolation and regression, and the genetic algorithm for optimization. It was found that the optimum configuration taking all the output operational parameters into account was stood up at the attack angle of 75, the mesh angle of 85.9, and the average inlet velocity of 0.0428 m/s. Also the global sensitivity analysis has been performed, which the average inlet velocity and the attack angle were obtained the most and the least effective parameters on optimum conditions, respectively. Due to the change in the velocity along the RO module with several SWM elements, the optimum performance was achieved by adjusting the geometric structure of the spacers with velocity variations in each RO element. (C) 2019 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.