OBJECTIVE This randomized controlled study compared acceptance and commitment therapy (ACT), cognitive-behavioral therapy (CBT), and a control group. METHODS 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). CONCLUSIONS 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.