INTRODUCTION: As Novel psychoactive substances (NPS) are conceived to mimic the effects of common illicit drugs, they represent a serious public health challenge due to the spike in intoxications and fatalities that have been linked to their use. This study aims to provide epidemiological data on NPS use in the USA, determining lifetime prevalence of use and defining demographic, socioeconomic, drug use patterns and mental health correlates. METHODS: This study uses secondary data from the US National Survey on Drug Use and Health (NSDUH), which is a large cross-sectional population-based survey carried out annually in the USA. We analysed data from 2007-14 (N = 307,935) using bivariate descriptive analysis and binary logistic regression to calculate prevalence and determine factors underlying NPS consumption. Adjusted odds ratios (OR) with 95% CI's were calculated for a set of selected independent variables. RESULTS AND DISCUSSION: Our analysis NSDUH from 2007-14 highlights an increase in NPS use among adults, especially among white young men aged 18 to 25. Although the level of education of NPS users was relatively higher as compared to non-users, NPS users seemed to have a less wealthy situation. However, socioeconomic vulnerability appeared to be less important than mental health issues as a correlate to NPS use. NPS users seem to have followed a pattern of polysubstance use throughout their life, which involves both traditional illicit drugs and classic synthetic drugs. As NPS use seemed to be more prevalent among people having mental health issues, the rise in their use may have a negative impact on population mental health outcomes. CONCLUSION: Further comparative research on trends in NPS use and potential public health responses would be instrumental for developing appropriate health interventions, including drug checking, education for users and training for healthcare professionals working both within emergency wards and in/outpatient addiction and mental health services.