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.