Vascular diseases, like peripheral arterial diseases (PAD) and coronary artery disease (CAD), are common diseases with a high morbidity. We investigated and compared the impact of these diseases on daily life using health-related quality of life (HRQOL) analysis. In 89 patients with PAD and 89 patients with multivessel CAD, the SF-36 was assessed before diagnostic staging and compared with an age-matched reference population. Both groups of patients had a significantly impaired HRQOL as compared to a reference population. Patients with PAD scored significantly (p 0.001) lower than those with CAD on the domains general health perception, change in health, physical functioning, social functioning, and pain. Patients with PAD have a reduced HRQOL in comparison with patients with CAD. Each disease has an impact on a specific domain of the HRQOL. Vascular disease mainly influences physical health.