BACKGROUND In recent years, there has been an increase in emergence and use of novel psychoactive substances (NPS) in the US and worldwide. However, there is little published epidemiological survey data estimating the prevalence of use in the US. METHOD Data on self-reported NPS use came from the National Survey of Drug Use and Health (2009-2013), a national representative sample of non-institutionalized individuals in the US. Subjects were asked to provide names of (non-traditional) drugs they used that they were not specifically asked about. We examined lifetime prevalence and sociodemographic correlates of self-reported use of new and uncommon synthetic drugs (NPS) among subjects ages 12-34-years-old. RESULTS 1.2% of subjects self-reported any use of the 57 NPS we examined. Use of psychedelic tryptamines (primarily DMT) was most common, followed by psychedelic phenethylamines (e.g., 2C series) and synthetic cannabinoids. Prevalence of self-reported use of NPS increased from 2009 to 2013 and use was most common among males, whites, older subjects, those of lower income, and among those residing in cities. Lifetime use of various other illicit drugs (e.g., LSD, cocaine, ecstasy/MDMA) was highly prevalent among NPS users. CONCLUSION This the first study reporting on use of a variety of NPS in a nationally representative US sample; however, use appears to be underreported as other national data suggest higher rates of NPS (e.g., synthetic cannabinoid) use. Developing more adaptable survey tools and systematically assessing NPS use would allow researchers to ask about hundreds of NPS and improve reporting as new drugs continue to rapidly emerge.