BACKGROUND: Health-related quality of life is an important factor to evaluate effects of different interventions in cardiovascular diseases. Improvement in quality of life (QOL) is an important goal for individuals participating in cardiac rehabilitation (CR) programs. The purpose of this study was to assess the impact of comprehensive CR on QOL in patients with cardiovascular disease (CAD). METHODS: In this quasi-experimental before-after study, the files of ۱۰۰ patients with CAD who were referred to rehabilitation department of Isfahan Cardiovascular Research Institute were studied using a consecutive sampling method. Data collection was performed from the patient's files including their demographics, ejection fraction, functional capacity, and resting heart rate. All patients participated in a comprehensive CR program and completed the validated questionnaire Short-Form ۳۶ Health Status Survey (SF-۳۶), before and after CR program. Data was analyzed based on sex and age groups (≥ ۶۵ and < ۶۵ years) using independent t-test and paired t-test (to compare variables between groups and before and after CR, respectively). RESULTS: After CR, scores of all physical domains of the SF-۳۶ including physical function (PF), physical limitation (PL), body pain (BP) and vitality (V) in addition to general health (GH) were significantly improved in all patients (P < ۰.۰۵) compared to the baseline. Patients with age < ۶۵ years had greater improvements in mental health (MH) and social function (SF) than patients with age ≥ ۶۵ years (P < ۰.۰۵). Women had greater improvement in PF, V and MH compared to men (P < ۰.۰۵). CONCLUSION: These results indicated that CR can improve QOL in cardiac patients especially in women. Elderly patients get benefit the same as other patients in physical domains. Keywords: Quality of Life, Cardiac Rehabilitation, Cardiovascular Diseases