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Climate change has been recognized as a significant threat for transportation infrastructure. The change in temperature profiles and precipitation patterns and the increase in the intensity of weather-related extreme events are among the effects attributed to climate change. Additionally, climate change may also alter the frequency and intensity of flood events, which increases the complexity of assessing the risk of bridge failure due to flood-related failure modes. Flood occurrence generally increases the rate of river bed erosion and may cause the formation of scour holes around bridge piers, leading to an increased risk of bridge failure. Several factors, such as future precipitation, basin parameters, flow direction, and drainage area, affect the streamflow of a river; accordingly, the proper prediction of long-term future flood hazard requires detailed and computationally expensive climate and hydrologic modeling, which can be prohibitive in assessing the life cycle risk of bridges and other transportation structures. This paper addresses these issues by proposing a comprehensive, yet computationally efficient, probabilistic framework for quantifying the risk of bridge failure due to flood events considering climate change. Statistical modeling was employed to draw a relationship between the downscaled climate data adopted from global climate models and the streamflow at a given location. The effects of different global climate models and carbon dioxide emission scenarios on failure risk due to flood hazard were taken into account. The results showed that using traditional assessment approaches that do not properly consider climate change effects can lead to a considerable underestimation or overprediction in the predicted future risk. The approach was applied to an existing bridge in Oklahoma; however, it is equally applicable to bridges and other transportation structures located in various regions in the United States.