Traditional seismic design codes have been developed and used for decades to stipulate the rules for earthquake-resistant design of structures. They are mainly based on the Force-Based Design (FBD) approach and on some linear elastic techniques. The inelastic seismic response of the structure is not directly addressed in the traditional seismic design codes. The initial aim of the current seismic design codes is public safety. In seismic codes, some information is provided regarding the damaged states of structural components, while limited information is provided regarding the damaged states of nonstructural members. In addition, no clear information is provided regarding economic losses and business interruption. The Performance-Based Seismic Design (PBSD) approach, a reliable approach for the seismic design of structures, is capable of providing more detailed information on the performance levels of both structural and nonstructural members and content systems. Some current seismic design codes adapted concepts of the PBSD approach in a deterministic manner, considering uncertainties implicitly. In this study, efforts have been made to develop a Probabilistic PerformanceBased Optimum Seismic Design (PPBOSD) methodology for Reinforced Concrete (RC) structures, considering uncertainties explicitly to provide a more practice-oriented approach. It is a powerful seismic design tool that provides structures with economical, robust, and rational design. In addition, structures designed using this approach could satisfy the target performance levels at multi-limit states. For the optimization problem, the objective function is given in terms of minimizing the expected total cost of the structure at a specific intensity level. Pacific Earthquake Engineering Research Center’s Performance-Based Earthquake Engineering (PEER PBEE) methodology is used for the performance assessment of the structure. The Endurance Time method is used in the PEER PBEE methodology framework while performing optimization. After the optimum solution is obtained, the Incremental Dynamic Analysis (IDA) method is used to verify the performance levels. The proposed methodology is applied to RC frame buildings with different numbers of stories. OpenSees software is used together with codes written in python for the design and analysis purpose.