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Background : Drug abuse in university students is an emerging social and health issue. The present study assesses alcohol and abuse of other illicit drugs and the adverse consequences related to such use and its relationship with self-care agency among European university students. Methods : A multicenter cross-sectional study was performed among 592 European students from different health science degrees. The screening of alcohol abuse was evaluated with the Alcohol Use Disorder Test (AUDIT), and the screening for substance-related risks and problems was conducted with the Car, Relax, Alone, Forget, Friends, Trouble (CRAFFT) screening test. We analyzed the relationship of substance abuse with self-care agency, assessed by the Appraisal of Self-Care Agency Scale (ASA). Results : 51.4% of the surveyed students reported alcohol intake, 16.6% of the students consumed both alcohol and cannabis, 1.6 % reported alcohol and other illicit drugs, and 3.7% consumed alcohol, marijuana, and other illicit drugs (73.3% of students reported alcohol intake alone or together with cannabis/hashish and/or other illicit drugs). The self-care agency scores were significantly different among groups in relation to certain sociodemographic factors such as gender ( p = 0.008) and country of residence ( p = 0.031). The self-care agency scores significantly correlated ( p = 0.001) with the personal motivations and consequences related to the consumption of drugs of abuse evaluated by the CRAFFT screening tool. Within the ASA domains, the most significant effects were observed regarding the subdomains of resources, awareness, and health behaviors. Conclusions : Self-care agency should be promoted to counteract the health and social consequences of the consumption of drugs of abuse among university students who will be future health care professionals.