Abstract High efficiency particulate air (HEPA) filters are widely used in various industries to contain airborne contamination. The pressure drop of the filters is a crucial performance parameter when designing a HEPA filter as it is the resistance that the filter offers to the flow of air. Thus, it is critical to find the effect of each configuration and integrate an optimal setup for the filter to avoid high-pressure drops. Set against these backgrounds, this study aims to study the effect of different configurations on the total pressure drop of the filter, and to review how each configuration can affect each other using a commercial software ANSYS Fluent. The different filter media pack configurations and boundary conditions investigated here are including pleat shape (V-shaped and U-shaped), pleat density (1-7 pleat/cm), pleat height (1cm, 1.3cm), and inlet velocity (0.02-0.2 m/s) on the pressure drop of the filter. A two-dimensional geometrical model is developed, and then validated with respect to the data obtained from Lydall M3004-06 property sheet. Upon successful validation exercise, a series of parametric studies is conducted to numerically examine the impact of changing each configuration on the total pressure drop of the filter. Results show that an optimal pleat density is attained where the total pressure drop is minimized, i.e., 3 pleat/cm for V-shaped and 4 pleat/cm for U-shaped for inlet velocity of 0.02 m/s. At a constant inlet velocity, the U-shaped pleat has a lower pressure drop than the V-shaped pleat at low pleat densities, but a higher pressure drop at higher densities. This behaviour can be attributed to the balance between inertial and viscous resistance. Increasing the inlet velocity increases the total pressure drop for all pleat heights and decreases the optimal pleat density. This effect is less pronounced on the V-shaped pleat. Increasing the pleat height for the U-shaped pleat decreases the pressure drop and optimal pleat density but increases pressure drop in the viscous dominated region. Conversely, increasing the pleat height for the V-shaped pleat decreases the pressure drop for all pleat counts and only decreases the optimal pleat density at high velocity.