Past research with North American participants has demonstrated a naturalness bias in the medical context: people prefer natural drugs to synthetic drugs under a variety of situations. Does such a bias exist in other countries (such as China) where cultural values and practices are quite different from those in the United States? We conducted 3 studies ( N = 1927) to investigate the naturalness bias with drugs and vaccines across cultures with American, Canadian, and Chinese participants. In studies 1A and 1B, participants chose or rated drugs (natural v. synthetic) for a hypothetical medical issue. The drugs were presented as having identical effectiveness and side effect profiles. Study 2 focused on a different medical context, vaccines, and required participants to rate their likelihood of taking vaccines (made from either more natural or more synthetic ingredients) for a harmful virus. The naturalness bias occurred across cultures in studies 1A and 1B, although it was not significant among Chinese participants in study 1B. In study 2, Chinese participants showed a stronger naturalness bias than Americans did, and safety concerns mediated the effect. Perceived safety accounted for the naturalness bias among Americans and Canadians, but did so only among Chinese in study 2. Overall, the results suggest that the naturalness bias in drug and vaccine decision making occurs across cultures, but Chinese participants may be more sensitive to the medical context. Highlights The naturalness bias — preferring natural to synthetic drugs or vaccines — occurred across cultures (Americans, Canadians, and Chinese). Chinese participants showed a stronger naturalness bias than Americans did when the medical context was focused on vaccination, and safety concerns mediated this effect. The naturalness bias may influence medical decision making across cultures, but Chinese participants may be more sensitive to naturalness in a vaccine context.