Reliable assessment of seismic performance of structural systems requires accurate and robust simulation techniques that can efficiently predict inelastic response in the large deformation range, up to structural collapse. This paper presents a real-time dynamic substructuring (RTDS) test program carried out on steel moment resisting frames (MRF) tested up to near collapse. A single-story, industrial building with steel MRFs at perimeter was examined applying the Loma Prieta earthquake record. Columns were pinned at their bases, while full stiffness and resistance was retained at beam-tocolumn joints. The physical substructure included only one column that was installed in the inverted position i.e. clamped at the base and pinned at the top: in this way only one lateral degree of freedom was involved in physical tests. The other column, the beam, building masses, gravity loads and damping forces were included in the numerical substructure. Time integration was performed using a variant of a Rosenbrock-W scheme implemented into the MathWorks's Simulink and XPC target computer environment. The tangent stiffness matrix of the structure was evaluated using different numerical strategies including data smoothing and filtering. Control techniques with constant or adaptive delay compensation for the feed-forward filter were implemented. The obtained results are compared and discussed to highlight the effect on structural response predictions. As a result, RTDS tests appear to be effective in the prediction of near collapse seismic response of steel frames, provided that robust numerical strategies are implemented.