<p>Personality traits significantly influence the development, persistence, and treatment outcomes of substance use disorders. Despite increasing addiction rates among women, sex-specific research remains limited. This study explores the relationship between addiction type and personality traits among inpatient women addicted to alcohol and opioids. A cross-sectional design included three groups: 80 women with alcohol addiction, 80 with opioid addiction, and 80 healthy controls. Participants completed the Revised Temperament and Character Inventory (TCI-5-R) and the Revised NEO Personality Inventory (NEO-PI-R). One-way ANOVA assessed group differences, and canonical discriminant analysis predicted group affiliation. Women with opioid addiction showed a distinct and maladaptive personality profile on both inventories compared to women with alcohol addiction and healthy controls, whereas women with alcohol addiction more closely resembled controls. According to Cloninger’s model, opioid-addicted women scored significantly higher on Novelty Seeking and Self-Transcendence, and lower on Self-Directedness and Cooperativeness (<i>p</i> &lt; 0.001). Within the Five-Factor Model, they also scored higher (<i>p</i> &lt; 0.001) on Neuroticism and lower on Agreeableness and Conscientiousness compared to alcohol-addicted women. Personality differences were more pronounced between women with opioid versus alcohol addiction than between alcohol-addicted women and healthy controls.</p>