This paper describes the practical application of computational analysis to the design of a reinforced concrete structure subject to blast loading from a vehicle-borne improvised explosive device. The structure includes a protective slab designed to provide a barrier between the blast load and a densely occupied commercial floor. The blast load derivation was carried out using commercially available computational fluid dynamics (CFD) (hydrocode) software to predict shock wave propagation, reflection and refraction effects. Pressure–time histories were extracted and applied to the mesh of a decoupled finite-element (FE) model of the structural system. The structural analysis was carried out using a commercially available explicit dynamic solver, incorporating non-linear material representations of the primary structural components including the protective slab and supporting columns, beams and walls. The analysis methodology was based on a macro level of structural detail commensurate with the design objectives, with column and beams represented with line elements and walls and slabs represented with thin shell elements. The computational analysis successfully confirmed the adequacy of the proposed design for the specified threat level. The paper concludes that the performance of a reinforced concrete structural system can be cost-effectively assessed for blast loading, to a level appropriate for design purposes, using existing commercially available CFD and FE tools.