Use of computational fluid dynamics (CFD) software packages within fire performance based engineering and risk assessment is increasing substantially. An important part in the process is validation and verification in order to be able to assess the accuracy and reliability of the computational tools. To improve the credibility of using CFD modeling in several high-consequence fields, such as the nuclear safety area, more work must be done. Fires in enclosures equipped with forced (or mechanical) interconnecting ventilation remain one of the key issues for fire safety assessment in the nuclear industry. The scenario of a fire in a confined and ventilated enclosure is a typical hazard during which the pressure may vary to an extent where it modifies the confinement levels and hence the safety of the installation. An understanding of the mechanisms leading to pressure variations during a fire scenario is of prime interest. In this paper an attempt to simulate several large-scale well-confined mechanically ventilated fire scenarios using Fire Dynamics Simulator (FDS) is presented. Full-scale experiments that have been performed within the PRISME project are compared to simulations done using a pre-release version of FDS 6. The behavior of the HVAC system has been the main focus in the comparison and it is demonstrated that FDS 6 is capable of predicting pressure induced phenomena in the ventilation system, both at inlets and exhausts, with satisfactory accuracy.