The study documents the characteristics of Hong Kong residents who used substances in mainland China. Characteristics of such users were compared with those using substances elsewhere. A cross-sectional survey was used. Data analyses were stratified by gender, and multivariate analyses were performed. Respondents, Hong Kong adults aged 18-30 (n=6,528), were interviewed using a mixed interviewer and computerized mobile phone method, at the Hong Kong-mainland China boundary. Cross-border substance users and other types of substance users had characteristics that were quite different (e.g., education level, perceived harmfulness of substance use in general, having friends who frequently used substances in mainland China). Crossboundary substance users also found it easier to obtain substances in mainland China than in Hong Kong (males: 60.5%, females: 39.6%) and perceived no chance of being arrested in mainland China because of substance use (men: 28.8%, women: 24.5%). They tended to use substances in discos/rave parties together with friends (men: 77%, women: 81%), and substances were often obtained for free (men: 63.2%, women: 78%). Ecstasy and ketamine were often used (men: 86.5% & 79.4%, women: 81% & 70.2%), and multiple uses of different substances were common (men: 81.3%, women: 68.6%). Lower price, peer influence, and better availability were reasons behind crossboundary substance use behaviors. Cross-boundary substance users have specific characteristics. Prevention policies should take these characteristics into account. Regional collaborations are highly warranted.