In this study, the appropriate cell type for periodic boundary conditions (PBC) in CFD analysis for spacer-filled membrane module design was validated by comparing the simulated values of pressure drop with that obtained by experiments. The pressure drop through spacer-filled channel depends on the geometric characteristics: angle, mesh size and filament diameter of the spacer and height, width, length and voidage of the channel. Results revealed that not all PBC types reported in the literatures were suitable to be used to analyze the fluid flow behavior in the asymmetric spacer system. Moreover, the prediction of pressure drop through full-scale membrane module can be estimated by the method of PBCs with a minimum cell numbers. The pressure drop through spacer-filled membrane module estimated by the method of PBCs with cell numbers of 18 x 8 agrees well with experimental data of a full-scale system within a deviation less than 7%.