Motivated by the early works on bidirectional interaction and the breakthrough to estimate seismic response to bidirectional shaking via unidirectional analysis, it is essential to answer the question: When is the interaction effect significant? Early works concluded that the effect of interaction is pronounced for stiff systems; consequently, the straightforward method for estimating seismic response to bidirectional excitation by using unidirectional analyses is verified primarily for short period systems. Hence, it is essential to identify the domain of significance for bidirectional interaction before adopting this simple methodology in design. Several parametrically defined systems with elastoplastic and degrading hysteresis models are studied under near-fault motions, assuming strength-independent and strength-dependent stiffness. The force-based and displacement-based analyses, conducted in parallel, reveal that the interaction effect is considerable for stiff systems, especially with degrading characteristics in a relatively low inelasticity range. However, the bidirectional effect may be significant even for highly flexible systems, especially for residual deformation, which in earlier works was shrouded. The range of significance depends on the hysteresis model, system parameters, and response indices. Regression analysis is carried out with the results of the case studies, and the derived regression models may be used for a preliminary assessment of the impact of interaction in advance.