A negative stiffness device has been tested within a quarter-scale highway bridge model on the seismic shaking table at the University at Buffalo Network for Earthquake Engineering Simulation (NEES) site. Based on the experiments, numerical models have been developed, calibrated, and used to simulate the response of the bridge under a wide range of ground motions. In addition, performance indices have been developed to systematically and quantitatively evaluate the relative performance of different isolation system configurations that employ combinations of positive and negative stiffness as well as various levels of positive damping. Further, the influence of boundary conditions (rigid versus flexible bridge piers) on the effectiveness of employing negative stiffness devices has been evaluated. Finally, concepts for graphical interpretation of the performance indices are presented and used to demonstrate the degree to which employing negative stiffness may be beneficial in improving the seismic response of bridge structures.