Abstract: A structure is usually designed with a relative higher column over-design factor (COF) to ensure that the structure satisfies strong-column-weak-beam (SCWB) design requirements. In this study, the theory of structural reliability is employed to investigate the most likely failure modes of reinforced concrete frame structures and the relative occurrence probability of an entire beam hinging failure mode considering the upper, middle, and lower collapse modes of structures. The analysis results of an example demonstrate that the middle collapse mode is the most likely failure mode with lower COF. If the value of COF is larger than 2.0, the upper collapse mode controls the collapse failure process of structures. This research can provide some useful guidelines for the collapse resistant design of structures under major or very rare earthquakes.