This study introduces an efficient procedure to estimate the structural response of a suspension bridge in real-time based on a limited set of measured data. Unlike conventional techniques, the proposed procedure does not employ mode shapes and frequencies. In this study, the proposed technique is used to estimate the response of a suspension bridge structure based on a set of strain gauge measurements. Finite element analysis is performed only once to set up the structural parameters, namely computed flexibility matrix, and computed hanger forces matrix. The response of the bridge was estimated without any additional finite element analysis using the computed structural parameters and the measured hanger strains. The Alfred Zampa Memorial Bridge, on Interstate 80 in California, was selected for this study. A high fidelity finite element model of the bridge was developed using the general purpose computer program ADINA. The proposed method has been proven to have the capability to estimate any type of structural response in real time based on the measured hanger strains, and provides an important part of an integrated Structure Health Monitoring (SHM) system for major bridges.