It is widely accepted that flexible foundations affect the responses of structures beneficially or detrimentally depending on the nature of input ground motion, the effective response periods and hysteretic and radiation damping of soil-foundation domain. In most analytical procedures, the effects of flexible foundation are accounted for by using lumped springs the properties of which are obtained from empirical data and relationships. Due to the wide variation in soil material characteristics and foundation configuration, the simplified approach may not represent the real performance with acceptable accuracy. In this paper, a typical bridge representative of the Central and Eastern U.S. inventory is analyzed with consideration of soil-structure interaction where embankments, abutments, and foundations are modeled in OpenSees (PEER Center) with three-dimensional finite elements. The bridge structure is modeled in Zeus-NL (MAE Center) with fiber frame elements. The two analysis platforms are combined through the multi-site multi-platform hybrid simulation framework, UI-SIMCOR. The fragility curves of the bridge are derived based on a most realistic analytical approach.