Indiana University-Purdue University Indianapolis (IUPUI) / The presence of a chronic pain condition can have a profound impact on one’s self-concept. Some individuals may have had to make major lifestyle changes. As a result, some people may start to define themselves in terms of their pain, such that their self-schema and pain-schemas become intertwined in a process termed schema-enmeshment. It is thought that schema-enmeshment is related to psychological distress making it a prime target for intervention. Little research has been conducted on interventions to reduce schema-enmeshment. Acceptance-based interventions may be especially appropriate in reducing schema-enmeshment or the connection between self and illness symptoms as these interventions tend to emphasize learning to live with pain and other symptoms and to work toward important life goals rather than continually fighting against the condition and allowing it to control their life. This study is a randomized trial comparing Acceptance and Commitment Therapy (ACT) to education about pain management in a sample of women with Fibromyalgia Syndrome (FMS). The primary aim of this study was to assess the efficacy of ACT in reducing schema-enmeshment between self and pain, as well as enmeshment between self and other symptoms and FMS as a whole. In addition, this study also explored the role of pain acceptance, specifically activity engagement as a mediator of the relationship between treatment group membership and changes in schema-enmeshment. The data was analyzed as an intent-to-treat analysis using the “last measure carried forward” method. Results indicated that the ACT group reported statistically significant differences in self schema-enmeshment with FMS, fatigue, and cognitive symptoms, but not with pain, following the intervention, compared to the educational control group. In each of these cases, the ACT group experienced greater reductions in schema-enmeshment compared to the education group. Interestingly, no statistically significant differences were observed for schema-enmeshment with pain. Statistically significant group differences were also observed for acceptance of pain following the intervention. Finally, a mediational model in which changes in activity engagement (a form of pain acceptance) served as the mediator of the relationship between treatment group and changes in schema-enmeshment with FMS was tested. The model was tested using a bootstrapping method, and results revealed a trend toward a significant indirect effect of changes in activity engagement leading to changes in schema-enmeshment with FMS. Taken together, the results of this study indicate that ACT may be a promising intervention for targeting maladaptive beliefs about the self in relation to illness, especially schema-enmeshment of self with illness and illness symptoms. Additionally, there is evidence that ACT may target key constructs such as activity engagement, which may be related to other cognitive and behavioral changes. Future directions for research and clinical practice related to ACT as an intervention for FMS are discussed in depth.