The role of soil-foundation-structure (SFS) interaction on seismic behavior of an elevated highway bridge (the I-880 viaduct) with deep foundations is investigated in this paper. A series of time domain, inelastic finite element simulations of seismic behavior of a bridge bent subjected to various earthquake events is carried out using two separate models of the system. The first model assumes the bridge columns to be rigidly connected to the foundation without SFS interaction. The second model incorporates SFS interaction through the use of equivalent springs. The spring properties are derived from three-dimensional finite element analysis of the pile foundation in a layered soil system. The analysis is based on nonlinear inelastic characteristics of the concrete substructure and linear elastic behavior of the soil-foundation system, which was determined to be a reasonable assumption for this case study. The ground motions used in the simulation studies describe the expected hazard at the site and represent earthquakes with a 10% probability of being exceeded in 50 years. Results of the analysis indicates that SFS interaction can have both beneficial and detrimental effects on structural behavior and is dependent on the characteristics of the earthquake motion.