A computer model has been developed to simulate the fluid flow in pleated filter cartridges. This model has been used to evaluate the performance and design of pleated cartridge membrane filters. The effects of medium compression, pleat deformation, and pleat crowding are analyzed. At higher flow rates due to the exerted fluid pressure the medium is deformed, which leads to a reduction in the material permeability. Further, due to pleating and bending there is a loss in effective filtration area. The combined effects of compression and reduction in filtration area cause deviations from Darcy's law. To interpret such deviations, permeability models based on the data obtained from the flat sheets of the filter material used in cartridge fabrication have been developed. The incorporation of the permeability model within the main hydrodynamic model determines the percentage loss in filtration area, percentage medium compression, and the pressure drop across the filters. Results of this study have been presented for fiberglass medium. The simulated results have been compared against experimental industrial data for purposes of model validation. The developed simulation tool offers a robust, cost-effective, and user-friendly design and analysis tool for pleated cartridge membrane filters, which can be easily used by engineers in industry.