In this work, a numerical 3D simulation of a longitudinal ventilation system (LVS) is developed to analyze the fire behaviour inside a road tunnel. The numerical modelling reproduces the Memorial Tunnel, a two-lane, 853 m long road tunnel, used for experimental purposes. On this tunnel, 98 full-scale fire ventilation tests with different ventilation systems were conducted, constituting the first significant experimental approach to analyze fire incidents inside road tunnels. A total number of 24 reversible jet fans were installed in groups of three, nearly equally spaced over the length of the tunnel, and cantilevered from the ceiling of the tunnel. The validation of a numerical model is developed in the present paper. For that purpose, the behaviour of the smoke generated during a fire incident inside a road tunnel is predicted and compared with previous experimental data collected in the Memorial Tunnel Project. The smoke evolution and the performance of the LVS is simulated with a commercial code, FLUENT, which allows 3D unsteady simulations of the Navier–Stokes equations for multispecies mixtures of gases. A sufficient mesh density was introduced for the spatial discretization in order to obtain accurate results in a reasonable CPU time. Hence, typical ratios between total number of cells and the overall tunnel length were employed in the modelling. As a result, good agreement was achieved in all the tested cases, defining an accurate methodology to predict the performance of a LVS in case of fire inside a tunnel.