BACKGROUND: The racial/ethnic composition of the United States is shifting rapidly, with non-Hispanic Asian-Americans, Native Hawaiians/Pacific Islanders (NHs/PIs), and mixed-race individuals the fastest growing segments of the population. We determined new drug use estimates for these rising groups. Prevalences among Whites were included as a comparison. METHODS: Data were from the 2005-2011 National Surveys on Drug Use and Health. Substance use among respondents aged ≥ 12 years was assessed by computer-assisted self-interviewing methods. Respondents' self-reported race/ethnicity, age, gender, household income, government assistance, county type, residential stability, major depressive episode, history of being arrested, tobacco use, and alcohol use were examined as correlates. We stratified the analysis by race/ethnicity and used logistic regression to estimate odds of drug use. RESULTS: Prevalence of past-year marijuana use among Whites increased from 10.7% in 2005 to 11.6-11.8% in 2009-2011 (P<0.05). There were no significant yearly changes in drug use prevalences among Asian-Americans, NHs/PIs, and mixed-race people; but use of any drug, especially marijuana, was prevalent among NHs/PIs and mixed-race people (21.2% and 23.3%, respectively, in 2011). Compared with Asian-Americans, NHs/PIs had higher odds of marijuana use, and mixed-race individuals had higher odds of using marijuana, cocaine, hallucinogens, stimulants, sedatives, and tranquilizers. Compared with Whites, mixed-race individuals had greater odds of any drug use, mainly marijuana, and NHs/PIs resembled Whites in odds of any drug use. CONCLUSIONS: Findings reveal alarmingly prevalent drug use among NHs/PIs and mixed-race people. Research on drug use is needed in these rising populations to inform prevention and treatment efforts.