Earthquakes are one of the most serious natural disasters. They not only cause fatalities and injuries, but also result in infrastructure damage, social effects, and economic impacts. Without appropriate preventive action plans and mitigation policies, unforeseen natural catastrophes can cause tremendous losses, as evident for the 2005 Hurricane Katrina in the southern coastal United States (particular in New Orleans) and the 1994 Northridge Earthquake in Southern California. However, policymakers generally focus only on the losses directly caused by the earthquake, or more specifically the direct losses caused from the destruction of the infrastructure. They tend to overlook the consequences from these losses, such as business disruptions or reductions in final demand. This study proposes an integrated framework to estimate the indirect economic loss due to damaged bridges within the highway system from an earthquake event. The framework is designed to be general and convenient to apply to other study regions. In this dissertation, a simulated earthquake scenario centered in St. Louis Missouri with a magnitude 7.0 was used as a case study. The research results have clearly shown that the indirect losses are significant when compared to the direct loss. Policymakers can apply this study framework and the results as a guide and decision tool for developing an appropriate preventive action plan to reduce the risk and potential losses before the earthquake occurs.