Pressure differential systems have the purpose of maintaining tenable conditions in protected spaces for different types of building safe places, like escape routes, firefighting access routes, lobbies, stairwells and refuge areas. The aim of pressure differential systems is to establish airflow paths from protected spaces at high pressure to spaces at lower or ambient pressure, preventing the spread of toxic gas released during a fire. This strategy ought to be supported by a detailed design of the necessary air supply, considering also the cycle of opening and closing doors during the egress phase. The paper deals with the design of a simple pressure differential system intended to be used in a building as a pressurized smokeproof enclosure. Specifically, experimental tests and numerical modelling are conducted with the objective of characterizing the pressure evolution in a small compartment under different conditions and through a cycle of door opening. Experimental tests are conducted in a simple 3-m side cubic enclosure with two doors and no vent openings. While a centrifugal fan blows constant airflow inside the structure, the pressure trend in time is recorded during steady state and transient conditions; additionally, the velocity of the airflow across the doors has been measured by means of an anemometer. Numerical CFD (computational fluid dynamics) simulations are carried out to reproduce the same smokeproof enclosure configuration (both geometrical and boundary conditions) using the fire dynamics simulator (FDS). Furthermore, specific attention is paid to the modelling of the leakage across the doors, directly inserted in the model through a localized HVAC (heating and venting air conditioning) advanced leakage function. Comparisons between experimental tests and numerical simulations are provided. Once the model was correctly calibrated, other geometrical and mechanical configurations have been studied, looking for convenient and efficient positions of the fan in order to fulfill the requirements of the pressure differential, airflow velocity and door handle force. The paper highlights some fundamental aspects on the pressurization and depressurization during steady state and transient phases, trying to identify if there are airflow profiles typical of some geometrical configurations. Full article