In railway bridges designed for freight transportation, dynamic phenomena are usually significant due to the regular repetition of axles, high loads, and track irregularities. Vehicle-structure dynamic interaction may affect trains’ stability due to the displacements and vibrations of the structure itself, which must be investigated using specific vehicle-structure interaction numerical methodologies. Besides regular operational conditions, traffic safety may also be threatened by external excitations such as crosswinds, earthquakes and others. Due to high wind speeds commonly observed in bridges, vehicle stability must be assessed properly to ensure train safety during crossing, especially for freight vehicles travelling in tare conditions. In this work, a three-dimensional numerical analysis of a railroad bridge crossed by a heavy-haul vehicle during crosswinds was performed using a train-track-bridge interaction methodology and considering realistic non-linear wheel-rail contact modelling. Numerical models of the bridge and vehicle were developed using finite element theory and multibody methodology, respectively, which were validated in previous works. Real vehicle and structural properties based on design and inspection data were considered. The case study is a 550-meter-long railway bridge composed of 22 simply supported steel-concrete composite spans, crossed by heavy-haul vehicles of the GDU gondola-type wagon with 325 kN axle loads. Artificially generated profiles of rail geometric irregularities based on the Federal Railroad Association power spectral density functions were used. Crosswinds were modelled according to stochastic wind field theory, where two-dimensional wind fields are generated over the length and height of the bridge, and wind speeds are calculated according to mean wind speeds and stochastic turbulent components in the vertical and lateral directions. Assessment of structural and train running safety was performed considering an average wind speed according to regional wind data and the most common operational train speed and load conditions. The behaviour of the bridge was assessed in terms of displacements and accelerations using reference limit values from design codes, while the safety of the vehicle was evaluated through indirect running safety indices such as those recommended in European codes as well as direct derailment coefficients based on vertical and lateral wheel-rail contact forces.