<p>A three-tower connected reinforced concrete (RC) frame building was selected as a prototype building and used to investigate resilience-based seismic design, aiming to provide a reference for multitower-connected buildings by using seismic isolation. First, a seismic resilience assessment strategy was recommended based on the characteristics of the case study. Specifically, the restoration cost index was recommended as the ratio of the total repair cost of multiple towers and connection parts with respect to the current replacement cost. In contrast, repair time and casualties were recommended as the longest repair time and the highest casualties of multiple towers due to their uncoupled functions. The influences of the critical design parameter of the isolation system (i.e., yield ratio) on the resilient performance of the entire building was investigated. Both the repair cost and time of the building decreased at decreasing yield ratios, which were attributed to the notable control of the maximum absolute floor acceleration. Only the case study, which showed a yield ratio of 2%, achieved the highest resilience level, as regulated by the relevant Chinese code. Hence, a 2% yield ratio is recommended for the conceptual design of seismically isolated multitower-connected buildings to achieve good seismic resilience.</p>