This paper investigates the pressure variations induced by a pool fire in a well-confined and force-ventilated enclosure. This study finds practical applications to fire safety in the nuclear industry in which some compartments are often highly confined and ventilated by means of a ventilation network. In this paper, the question is to study and understand whether the pressure effect could be high enough to cause fire barriers to fail (fire door, dampers, etc.) and/or to release radioactive material inside the nuclear facility in spite of the pressure drop cascade strategy usually considered. Relying on two sets of large-scale fire tests performed by IRSN, this work quantifies and discusses the impact of pressure effects caused by hydrocarbon pool fires on the fire compartment and on the ventilation network. Pressure histories are presented for experiments involving 0.3–3.1-MW liquid pool fires and a fire room connected to an industrial ventilation system that includes both inlet and exhaust branches. The analysis of experimental data is supported with a theoretical approach in order to describe in detail the physical mechanisms that contribute to pressure variations. Then, a parametric analysis allows us to determine the effects of the fire heat release rate and the air flow resistance inside the ventilation network on the pressure peaks. Finally, the last part of this paper focuses on a correlative approach to estimate the overpressure peak at fire ignition. ► Investigation of pressure variations from experimental and theoretical approaches. ► Physical mechanisms that induced pressure peaks at ignition and extinction. ► Parameters are the fire, the ventilation network set-up and the enclosure properties. ► Experimental correlation for the prediction of overpressure peak at fire ignition.