Objective: To obtain comparable data on knowledge, attitudes, and practices of high school students (16 years old) in the use of new psychoactive substances (NPS) and illicit drugs, thus making it possible to outline some trends in consumption patterns at this age. Methods: This study is based on the data collected within the European School Survey Project on Alcohol and Other Drugs (ESPAD)1 framework in 2011. The Romanian sampling frame included high school students in both grades 9 and 10, from 149 schools and 268 classes. The sampling frame has national representatives of students at regular schools and covered all 42 districts of the 8 regions. We investigated all the drugs considered illicit according to Romanian laws. Results: The use of any type of illicit drug or NPS at least once in their lifetime was 19.2%, with the gender distribution as follows: 22.1% among boys and 16.8% among girls. The most frequently experimented drugs were cannabis and inhalants with a prevalence of 7.2% followed by NPS 5.3%. Regarding the age of onset of use of drugs, the highest rate of adolescents starting drug use was at the age of 13 or earlier in the case of inhalants: 1.8% of the total number, followed by cannabis and NPS: 0.8%. The risk of regular use, regardless of the drug type, is perceived as being high by most of the respondents, the proportions varying between 66% and 72%. The perception of high risk in the case of experimental use for the illicit drugs varied between 40% and 47% but only 28% for NPS. Of those who used illicit drugs, 69.1% have indicated curiosity as main motivation, 21.6% indicated the wish to change their mood, and 17% declared that they wanted to forget about their problems. The same classification was recorded in NPS use. Conclusion: The result of the national study (ESPAD) ranks Romania in the last 10 European countries with regard to the level of prevalence of illicit drug and NPS use at least once in their lifetime among 16-year-old pupils.