Abstract: In this paper, single-mode and multi-mode control of the seismic response of multistory structures with MTMD is investigated. The multistory structures are predigested as MDOF systems in series. Response is obtained using the absolute value of transfer function of harmonic response of structure in the frequency domain, which is deduced by means of three different methods. In the first method, the differential equation of structure system with MTMD is given and transformed from time domain into frequency domain. The transfer function in frequency domain is obtained. In the second method, the reaction of MTMD to structure and the earthquake load are taken as input of structure. The transfer function is deduced considering structural mode coupling. In the third method, the transfer function is obtained considering structural mode uncoupling. Inertia mass participation coefficient is presented which elucidates the action mechanism between MTMD and structure. They are illustrated, and compared with the dynamic time history analysis result. For control of multistory structures with MTMD, multi-mode control is superior to single-mode control. For analysis precision, considering modes coupling is superior to doing mode uncoupling. For shearing model, the result with uncoupling meets the engineering demand.