This paper concentrates on the fragility analysis method for vertically plan reinforced concrete frame structures. The weakness story inter-story drift ratio is selected as the fragility variable for vertically plan structures. Five states are established to distinguish the structural seismic performance levels, which are expressed with inter-story drift ratio. Then through the nonlinear dynamic analysis and linear regress, the exceeding probability function of seismic response is obtained and a new fragility analysis method is put forward for vertically irregular frame structures. Two kind of unit models, two kind of hysteretic models and forty earthquake records are chosen to established structure-earthquake system samples. Thus one hundred and twenty structure-earthquake system samples are obtained for irregular reinforced concrete frame, which take into account the uncertainty of member materials, structures systems, numerical simulation models and earthquake motions adequately. Then example is presented to demonstrate the applicability and utility of the proposed methodology. Seismic performances of a vertically irregular reinforced concrete frame structure are evaluated in detail. It is concluded that fragility curves are more abrupt in low input earthquake motion intensity and they are influenced much by the structural performance levels.