The Yangtze River Delta (YRD) is the area with the densest high-speed railway (HSR) network in China, and it leads the high-quality economic development (HQED) in the country. HSR plays an important role in regional development. However, research on the impact of the HSR on HQED is notably limited. Theoretically, this study develops an analytical framework for the mechanism of the HSR’s influence on HQED. Empirically, it calculates the HQED index and then investigates the impact of the HSR on HQED and the regional discrepancies across cities in the YRD, based on data from 2011 to 2019 using the difference-in-differences model. The results show: (1) The mechanism lies in that the HSR improves urban accessibility, accelerates the flow of the production factors, and enhances the allocation efficiency of the input factors. (2) The distribution of the HQED level presents an obvious circular pattern, with Shanghai and Suzhou at the centre, showing the prominent principle of distance decay. (3) Both the regression model and the robustness tests show that the HSR significantly promotes HQED in the YRD. Additionally, the economic development, foreign capital spent, financial level, industry advancement, and living standard are conducive to HQED. (4) The results of the heterogeneity test reveal that the HSR has an obviously varied impact on HQED in cities depending on their size and location. The HSR has a significant promotional effect on HQED in cities with a large population and those far away from a provincial city.
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