Abstract INTRODUCTION: The purpose of this study was to determine the effect of cognitive-behavioral therapy on anxiety reduction and improvement of quality of life in patients with cardiovascular disease. methods: The statistical population comprised patients with coronary artery disease (CAD) in Isfahan in 2006. Fifty-six CAD patients referring to Chamran Heart Center and Isfahan Cardiovascular Research Center (ICRC) were randomly selected and assigned to control and case groups. The case group underwent cognitive-behavioral therapy (CBT) in 8 two-hour structural sessions. Patients in both case and control groups completed Cattel anxiety questionnaire and Mc new life quality questionnaire, which are specific for patients with cardiac disease before, and 2 weeks after therapy. The control group only completed the questionnaires without therapy. Both groups completed another questionnaire, which obtained demographic information. results: Based on the results, cognitive-behavioral therapy in the case group led to reduced anxiety and improved quality of life (P<0.000). Our findings showed the effectiveness of cognitive-behavioral therapy in reducing hidden and manifest anxiety (P<0.000) and improving the quality of life, as well as emotional, physical, and social function (P<0.000) in patients with cardiovascular disease. CONCLUSIONS: We recommend that methods for anxiety reduction and improvement of quality of life be taught to CAD patients via cognitive-behavioral therapy programs. Keywords: Cognitive-behavioral therapy, anxiety, quality of life, cardiovascular disease.