Objective: The aim of this study was to investigate the mediating role of stressful life events in the relationship between personality traits and addiction readiness. Method: The research method was correlational descriptive of structural equation modeling type. The statistical population included all substance-dependent women referring to addiction treatment clinics in Yazd in 2019-2020. Among them, 120 individuals were selected by convenience sampling method. Participants completed the addiction potential scale, the stressful life events scale, and the NEO personality questionnaire. Results: The proposed model had an appropriate fit. Neuroticism, agreeableness, conscientiousness, and stressful life events had direct and significant relations to addiction readiness. Also, stressful life events mediated the relations of neuroticism, extraversion, agreeableness, and conscientiousness to addiction readiness. Conclusion: The result of the present study, in addition to explain the internal and external factors affecting the addiction readiness in women, can be useful for the prevention and treatment of addiction.