Residential mobility has been an important topic in public health for the past decades. More than 22 million Americans migrated from state to state in 2000, but characteristics of minority American movers are not well documented in the aspect of public health. Using the U.S. national survey, we examined the association between residential mobility and gateway drug use among Hispanic adolescents in the U.S. Frequent movers and never movers were compared in the study. The study results indicate that frequent movers (moved more than 4 times for the past 5 years) were more likely than never movers to smoke and use marijuana. We also found that frequent residential relocation, females, and older teenagers (14-1714, 15, 16, 17) are risk factors of gateway drug use among Hispanic adolescents.