BACKGROUND Acceptance and Commitment Therapy is the third wave therapy with the greatest empirical evidence in the treatment of drug abuse. METHODS Thirty-one women with substance use disorder (SUD) were randomly assigned to two conditions, an intervention based on Acceptance and Commitment Therapy (ACT) and a control group on a waiting list. All participants were assessed three times (before treatment, at the end, and at a six-month follow-up) using urinalysis, the Mini International Neuropsychiatric Interview (MINI), the Addiction Severity Index (ASI-6), the Anxiety Sensitivity Index, and the Acceptance and Action Questionnaire (AAQ-II). RESULTS After 16 ACT intervention sessions, abstinence rates of 27.8% were observed, increasing to 43.8% after six months. The treatment also promoted improvements in other areas, such as reductions in the percentage of comorbid psychopathology and anxiety sensitivity, and the increase of psychological flexibility, which, in general, were not documented in the comparison group. CONCLUSIONS Clinical gains were achieved, and we consider ACT to be an effective and appropriate treatment to be applied in the prison context.