OBJECTIVES: To investigate the differences in vaccine hesitancy and preference of the currently available COVID-19 vaccines between two countries, namely, China and the United States (U.S.). METHOD: A cross-national survey was conducted in both China and the United States, and discrete choice experiments, as well as Likert scales, were utilized to assess vaccine preference and the underlying factors contributing to vaccination acceptance. Propensity score matching (PSM) was performed to enable a direct comparison between the two countries. RESULTS: A total of 9077 (5375 and 3702 from China and the United States, respectively) respondents completed the survey. After propensity score matching, over 82.0% of respondents from China positively accepted the COVID-19 vaccination, while 72.2% of respondents from the United States positively accepted it. Specifically, only 31.9% of Chinese respondents were recommended by a doctor to have COVID-19 vaccination, while more than half of the U.S. respondents were recommended by a doctor (50.2%), local health board (59.4%), or friends and families (64.8%). The discrete choice experiments revealed that respondents from the United States attached the greatest importance to the efficacy of COVID-19 vaccines (44.41%), followed by the cost of vaccination (29.57%), whereas those from China held a different viewpoint, that the cost of vaccination covered the largest proportion in their trade-off (30.66%), and efficacy ranked as the second most important attribute (26.34%). Additionally, respondents from China tended to be much more concerned about the adverse effect of vaccination (19.68% vs. 6.12%) and have a lower perceived severity of being infected with COVID-19. CONCLUSION: Although the overall acceptance and hesitancy of COVID-19 vaccination in both countries are high, underpinned distinctions between these countries were observed. Owing to the differences in COVID-19 incidence rates, cultural backgrounds, and the availability of specific COVID-19 vaccines in the two countries, vaccine rollout strategies should be nation-dependent.