This paper introduces a comprehensive framework to assess the regional economic impacts of high-speed rail (HSR) in China with a focus on its long-term implications. This research has two major research highlights: First, the regional impacts of HSR are evaluated under a dynamic and spatial (multiregional) general equilibrium modeling framework. Such a framework provides a comprehensive understanding of the impacts with variations in both space and time. Second, the assessment provides a demonstrative example of an ex post evaluation of the impacts based on the actual rail infrastructure investment data for the period of 2002 – 2013 using on a dynamic recursive multi-regional CGE model. The research findings confirm that rail infrastructure development in China has a positive regional economic impacts with a gross output multiplier of 1.01 and a GDP multiplier of 0.1 in the long-run. The aggregate impacts were found to be the highest in the southwest region, whereas the impacts are relatively small in developed eastern regions. The research findings provide implications for future HSR development in both China and other countries.