<p>Background: Schizotypy is a key risk factor for psychosis-like experiences and for identifying those at high risk for schizophrenia spectrum disorders. However, there is little research on schizotypy measures among people who use substances. This study examined the validity of the Oviedo Schizotypy Assessment Questionnaire-Abbreviated (ESQUIZO-Q-A) in adolescents and young adults who use substances. Methods: A total of 4,360 participants who reported alcohol, tobacco, or cannabis use in the previous 30 days were assessed. Exploratory and Confirmatory factor analyses were conducted to examine the internal structure of the questionnaire. Invariance across sex and age were examined. Validity evidence was gathered through correlations and network analysis with measures of substance use disorder (SUD) risk, positive emotional dysregulation, suicidal behavior, and emotional disorder risk. Results: The findings support a bifactor model with three specific dimensions (anhedonia, interpersonal disorganization, and reality distortion) and a general factor that exhibited invariance across sex and age. Reliability was strong [α: anhedonia = 0.82, α: reality distortion = 0.82, α: interpersonal disorganization = 0.80]. Validity was supported by associations with emotional disorder risk (|r| = 0.155-0.539), suicidal behavior (|r| = 0.049-0.403), positive emotional dysregulation (|r| = 0.081-0.417), and SUD risk (|r| = 0.014-0.236). All ESQUIZO-Q-A dimensions were directly associated with suicidal behaviors, with interpersonal disorganization showing the strongest associations. Conclusions: The ESQUIZO-Q-A is a valid and reliable instrument for assessing schizotypy in young individuals who use substances. Its use in prevention and treatment settings may facilitate the early identification of individuals at heightened risk for severe mental health outcomes.</p>