This work presents results from a numerical investigation on the influence of fluid-structure interaction (FSI) on the dynamic response of thin steel plates subjected to blast loading. The loading was generated by a shock tube test facility designed to expose structures to blast-like loading conditions. The steel plates had an exposed area of 0.3 m × 0.3 m and experienced large deformations during the tests. Numerical simulations were performed using the finite element code EUROPLEXUS. An uncoupled FSI approach was compared to a coupled FSI approach in an attempt to investigate FSI effects. Reduced deformation was observed in the plates due to the occurrence of FSI during the dynamic response. The general trend was an increased FSI effect with increasing blast intensity. The numerical results were finally compared to the experimental data to validate their reliability in terms of deflections and velocities in the steel plates. A good agreement with the experimental data was found, and the numerical simulations were able to predict both the dynamic response of the plate and the pressure distribution in front of the plate with good accuracy. Hence, the numerical framework presented herein could be used to obtain more insight regarding the underlying physics observed in the experiments. The clear conclusion from this study is that FSI can be utilized to mitigate the blast load acting on a flexible, ductile plated structure, resulting in reduced deformations.