Use of new psychoactive substances (NPS) across Europe remains a public health challenge. The study describes potentials and limitations of methods in a transnational survey of recent marginalised, nightlife and online community NPS users in Germany, Hungary, Ireland, the Netherlands, Poland and Portugal (n = 3023). In terms of demographic profile, drug use history and type of NPS, different methods reached different segments of the NPS-using population. Last year use of different NPS varied across countries and groups. Respondents used NPS in a variety of settings, with public spaces most common in the marginalised group. The study suggests that prevalence rates can reveal a picture of the NPS market that significantly deviates from what law enforcement seizures indicate. Outreach in nightlife settings and peer education are recommended to inform users about health risks and to improve access to drug services and care.