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Background: Personality traits, such as self-directedness (SD) and cooperativeness (CO), may be indicative of problematic alcohol and/or drug use., Objectives: The aim of this study was to quantify the association of substance use with SD and CO in a large cohort of adolescents., Method: A total of 6,917 individuals (58% women) at the age of 18 who had filled in the Alcohol Use Disorder Identification Test (AUDIT) and Drug Use Disorder Identification Test (DUDIT), and the SD and CO scales from the Temperament and Character -Inventory, as part of the Child and Adolescent Twin study in Sweden were included in the analyses., Results: High AUDIT scores (>15) were found in 2.4% of the population and high DUDIT scores (>7) in 1.2% of the population. Total score on the AUDIT was negatively correlated (p < 0.001) with SD (r = -0.18) and CO (r = -0.15), as well as total DUDIT with SD (r = -0.11) and CO (r = -0.08). The risk of high AUDIT (>15) and DUDIT (>7) was highest for those with a low (1 standard deviation below mean) SD score (ORs 4.1 and 4.5, p < 0.001) and a low CO score (ORs 3.5 and 4.5, p < 0.001). However, at 1 standard deviation above mean, no association between alcohol or drug use and SD or CO was seen. Using SD and CO scores to predict AUDIT >15 or DUDIT >7 yielded a sensitivity between 62.4 and 71.3% and a specificity between 64.9 and 70.4%., Conclusions: Personality traits of low SD and CO are associated with increased alcohol and drug use. These findings support the notion that personality traits can be used to identify individuals at high risk of substance abuse., (The Author(s). Published by S. Karger AG, Basel.)