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Objectives: This randomized controlled study compared acceptance and commitment therapy (ACT), cognitive-behavioral therapy (CBT), and a control group. Method: The participants were 50 incarcerated women diagnosed with current substance use disorder. Two psychologists carried out pre- and posttreatment assessment and a 6-month follow-up assessment using the following instruments: Anxiety Sensitivity Index, Addiction Severity Index-6, Mini International Neuropsychiatric Interview, and Acceptance and Action Questionnaire. Results: The study shows that the women who received treatment benefited differentially from the interventions. At posttreatment, CBT was more effective than ACT in reducing anxiety sensitivity; however, at follow-up, ACT was more effective than CBT in reducing drug use (43.8 vs. 26.7%, respectively) and improving mental health (26.4% vs. 19.4%, respectively). Conclusion: ACT may be an alternative to CBT for treatment of drug abuse and associated mental disorders. In fact, at long-term, ACT may be more appropriate than CBT for incarcerated women who present serious problems.