Aiming to develop and implement intervention strategies targeting pharmacological neuroenhancement (PN) among university students more specifically, we i) assessed the prevalence of PN among German university students, ii) identified potential sociodemographic and study-related risk groups, and iii), investigated sociodemographic, psychological, study-related psychosocial, general psychosocial and health behavior related factors predicting the 12-month prevalence of PN. Therefore, a cross-sectional online survey was administered to all students of the University of Mainz, Germany. A binary logistic regression with stepwise inclusion of the five variable groups was performed to predict PN.A total of N = 4,351 students participated in the survey of which N = 3,984 answered the question with regard to PN. Of these, 10.4% had used one substance for PN at least once in the past 12 months. The regression revealed 13 variables that were significantly related to the 12-month prevalence of PN.Specifically, the group of health behavior variables had the strongest influence on the explained variance of PN. Therefore, an approach to the prevention of PN should be multifactorial so that it addresses social conditions, as well as education on substance use and healthy behaviors in terms of non-pharmacological strategies as alternatives of PN.