A series of large-scale real-time hybrid simulations (RTHSs) are conducted on a 0.6-scale 3-story steel frame building with magneto-rheological (MR) dampers. The lateral force resisting system of the prototype building for the study consists of moment resisting frames and damped brace frames (DBFs). The experimental substructure for the RTHS is the DBF with the MR dampers, whereas the remaining structural components of the building including the moment resisting frame and gravity frames are modeled via a nonlinear analytical substructure. Performing RTHS with an experimental substructure that consists of the complete DBF enables the effects of member and connection component deformations on system and damper performance to be accurately accounted for. Data from these tests enable numerical simulation models to be calibrated, provide an understanding and validation of the in-situ performance of MR dampers, and a means of experimentally validating performance-based seismic design procedures for real structures. The details of the RTHS procedure are given, including the test setup, the integration algorithm, and actuator control. The results from a series of RTHS are presented that includes actuator control, damper behavior, and the structural response for different MR control laws. The use of the MR dampers is experimentally demonstrated to reduce the response of the structure to strong ground motions. Comparisons of the RTHS results are made with numerical simulations. Based on the results of the study, it is concluded that RTHS can be conducted on realistic structural systems with dampers to enable advancements in resilient earthquake resistant design to be achieved. Copyright © 2014 John Wiley & Sons, Ltd.