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In this article, we critically review the development and implementation of COVID-19 vaccination in Singapore and China during the pandemic. Methods: We collect and analyze data from a range of sources, including scholarly articles, statistics and documents from national governments in the two countries, and reports from international organizations. Results: There are important differences in the two countries’ approaches to the evolving pandemic, and thus the roles that COVID-19 vaccination plays in the overall response strategies in these two countries. Conclusions: Whereas Singapore adopted a “living with the virus” strategy, China continued to pursue a COVID-zero strategy. The overall COVID-19 response strategy of Singapore was largely shared by many countries in the world, while that of China was more unique and hardly imitated elsewhere. Nevertheless, vaccination played a significant role in both countries’ responses to the pandemic. A comparison and contrast between the vaccination processes in these two countries thus shed important light on the drivers and outcomes of COVID-19 vaccination in different settings.