Treatment for comorbid substance use disorder (SUD) and posttraumatic stress disorder (PTSD) is of particular relevance for incarcerated women, whose rates of PTSD and SUD are considerably higher than women in the general population. Yet virtually no treatments have been developed or systematically evaluated that target concurrently the symptoms of PTSD and SUD in this underserved population. This preliminary study evaluates the initial efficacy of a cognitive-behavioral treatment, Seeking Safety, as an adjunct to treatment-as-usual in an uncontrolled pilot study of incarcerated women with current SUD and comorbid PTSD. Of the 17 incarcerated women with PTSD and SUD who received Seeking Safety treatment and had outcome data, results show that nine (53%) no longer met criteria for PTSD at the end of treatment; at a followup 3 months later, seven (46%) still no longer met criteria for PTSD. Additionally, there was a significant decrease in PTSD symptoms from intake to posttreatment, which was maintained at the 3-month followup assessment. Based on results from a diagnostic interview and results of urinalyses, six (35%) of the women reported the use of illegal substances within 3 months from release from prison. Measures of client satisfaction with treatment were high. Recidivism rate (return to prison) was 33% at a 3-month followup. Overall, our data suggest that Seeking Safety treatment appears to be appealing to incarcerated women with SUD and PTSD and that the treatment has the potential to be beneficial, especially for improving PTSD symptoms. However, these findings are tentative given that there was no control group.