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This random assignment study compared women in a prison Therapeutic Community (TC) program with those in a cognitive-behavioral intervention. Over two thirds of study subjects received a lifetime diagnosis of severe mental disorder, nearly one-half received a diagnosis of PTSD, and virtually all reported exposure to trauma. Preliminary analysis (n = 314) found significantly better six-month post-prison outcomes for the TC group on measures of mental health, criminal behavior and HIV-risk behavior. These findings suggest the short-term effectiveness of prison TC treatment for female offenders with substance use disorders, and underscore the importance of adapting treatment to address mental health.