Abstract: In China, the economy has entered the stage of high-quality development. As the main bearing form of regional economic development, how to improve the level of regional integration and promote the high-quality development of urban agglomeration economy has become a hot spot of regional economic research. In this paper, the Yangtze River Delta City Economic Coordination Committee as a mechanism of regional cooperation is regarded as a quasi natural experiment. Through the double difference method, an empirical model is established to investigate the impact of regional integration on the high-quality economic development of the Yangtze River Delta city cluster, and its heterogeneity and mechanism are discussed in depth. The research shows that regional integration improves the overall quality of economic development of the Yangtze River Delta urban agglomeration, and the robustness test also supports this conclusion. The heterogeneity test shows that regional integration promotes the quality of economic development of the original cities and new cities in the Yangtze River Delta, and the promotion effect is greater in the original cities than in the new cities. The mechanism test shows that regional integration can promote the high-quality economic development of the whole city, the original city and the new city through the market integration mechanism and the industrial structure upgrading mechanism, but the role of the economic linkage mechanism has regional differences.