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This study assessed preferences for hypothetical vaccines for children in 2 large vaccine markets according to how the vaccine-preventable disease is transmitted via a discrete choice experiment. Surveys in China (N = 1350) and the United States (N = 1413) were conducted from April to May 2021. The discrete choice experiment included attributes of cost, age at vaccination, transmission mode of the vaccine-preventable disease, and whether the vaccine prevents cancer. Preference utilities were modeled in a Bayesian, multinomial logistic regression model, and respondents were grouped by vaccine preference classification through a latent class analysis. Individuals favored vaccines against diseases with transmission modes other than sexual transmission (vaccine for sexually transmitted infection [STI] vs airborne disease, in the United States, odds ratio 0.71; 95% credible interval 0.64-0.78; in China, odds ratio 0.76; 95% credible interval 0.69-0.84). The latent class analysis revealed 6 classes: vaccine rejecters (19% in the United States and 8% in China), careful deciders (18% and 17%), preferring cancer vaccination (20% and 19%), preferring vaccinating children at older ages (10% and 11%), preferring vaccinating older ages, but indifferent about cancer vaccines (23% and 25%), and preferring vaccinating children at younger ages (10% and 19%). Vaccine rejection was higher with age in the United States versus more vaccine rejection among those at the age of 18 to 24 and ≥ 64 years in China. The public had strong preferences against giving their child an STI vaccine, and the class preferring a cancer vaccine was less accepting of an STI vaccine. Overall, this study points to the need for more education about how some STI vaccines could also prevent cancers. • Countries have had mixed success rolling out vaccines for sexually transmitted infections (STIs). For example, human papillomavirus vaccination lags behind hepatitis B vaccination. • Individuals in the United States and in China had consistently strong dispreferences for STI vaccines, although the 2 countries varied in terms of what proportion and what groups would reject vaccines altogether. • Rollout of future STI vaccines should also consider preferences for when the vaccine be administered and what chronic diseases the vaccine prevents. [ABSTRACT FROM AUTHOR]