Abstract: Coronary artery disease (CAD) is the major cause of death in the United States, resulting in one in every five deaths each year. Psychosocial factors increase one's risk of heart disease, yet the mechanisms by which this relationship operates remain unclear. Attention has been given to the role of the chronic and excessive inflammation in the pathogenesis of heart disease. Researchers have demonstrated relationships between psychosocial risk factors and pro-inflammatory cytokines, providing a possible mechanism between psychosocial risk and CAD. The purpose of this study was to investigate whether inflammatory processes mediate the relationship between psychosocial risk factors and CAD. Forty CAD participants were recruited from Scripps Hospital and randomized to an intervention group, receiving an 8 week psychosocial skills building/stress management group, or a control group. The following psychosocial variables were measured pre- and post-intervention: hostility, by the Cook-Medley Hostility Scale (Ho); anger, by the State-Trait Anger Expression Inventory - 2 (STAXI-2); depression, by the Center for Epidemiological Studies - Depression scale (CES-D); and social support, by the Interpersonal Support Evaluation List (ISEL). Levels of the inflammatory markers, high-sensitivity CRP (hsCRP), IL-6, and TNF-α, were also measured pre- and post-intervention. Thirty-three of the enrolled participants completed the study. Hierarchical multiple regressions revealed that group assignment significantly predicted improvements in Trait Anger (p < .01), Anger Out (p < .01), Anger Control-In (p = .02), and overall psychosocial risk, as measured by a Composite variable ( p = .02). Group assignment did not significantly predict change in CRP or IL-6. Contrary to the study hypothesis, control group assignment significantly predicted decreased TNF-α (p = .03). There was no support for mediation of inflammation change by psychosocial improvement. The results suggest that psychosocial risk factors of CAD can be reduced by an 8 week psychosocial treatment, but this improvement may not influence inflammatory cytokines believed to be involved in CAD.