Most international design codes consider the nonlinear seismic performance of a structure by the concept of reduction/modification factor (R). Then, an elastic static force-based method can be normally used for seismic design to create earthquake resistant RC buildings. The response modification factor (R) is sensitive to many aspects such as overall ductility, over-strength, damping, and redundancy levels. Indeed, these factors are severely affected by geometric irregularity of the structural system. So, R-value does not become a constant number for the all types of structures with the same lateral load resisting system, as many standard codes noted. It depends on types, combination, and degrees of geometric vertical irregularity. This research assesses the actual values of R for regular and familiar vertical irregularity cases in RC buildings with moment-resisting frames (MRF) systems. Also, it takes into account the reduction percent that may occurs in R-value due to these studied vertical irregularities. The vertical irregularity cases, such as set-back and soft story, are essentially needed to be studied greater than ever due to the wide propagation of these types of buildings in Egypt, recently. In addition, the potential analytical methods that may be used to calculate R-value in comparison with Egyptian code’s value. Nonlinear static pushover analysis is carried out using ETABS via three-dimensional numerical models. The findings prove that vertical irregular models have poor seismic capacities, in comparison with regular one, due to their sudden change in lateral stiffness than that with regular aspect. So, the response modification factor (R) must be re-calculated or even scaled-down before design stage with 15% and 25% for single and combined vertical irregularity, respectively. In addition, this investigation derives a vital equation between R values with vertical irregularity ratios in each studied model. This equation shall be a guide for seismic design codes, structural design engineers, and researchers. Accordingly, the response modification factor R does not become a fixed value regardless vertical irregularity aspects of the buildings, but it has a variable value that depend on their inelastic seismic performance of the lateral load resisting systems.