Introduction: The use of psychoactive substances has been frequently associated with cognitive impairment. More and more people, including adolescents, use the plant hallucinogen beverage “ayahuasca” throughout the world. Long-term ayahuasca use by adolescents might eventually result in impaired cognitive performance. Objective: The objective of this study is to assess neuropsychological performance of adolescents who consume ayahuasca within a religious ritual setting. Method: Forty ayahuasca consuming adolescents and forty adolescents who never used ayahuasca were compared on their performance on a battery of neuropsychological tests. Groups were matched by sex, age, and educational level. Results: Both groups performed well on all neuropsychological tests. However, there were differences between the groups. Controls outperformed subjects on more complex tests, that is, those requiring more cognitive functions to perform a specific task. Conclusions: Adolescents who consume ayahuasca performed well on all the neuropsychological tests. However they did not perform as well as the control group whenever extra cognitive strength was required. It is possible that ayahuasca may have some subtle effect on cognition that can only be observed before highly demanding tasks. However, other variables may have interfered with these findings.