The diabetic foot reduces the health-related quality of life (HRQoL) in patients with diabetes mellitus. This study aims at ascertaining the impact of the etiological factors of the diabetic foot on the various aspects of HRQoL. This is a comparative study involving type 1 or type 2 (n = 421) diabetic patients divided into 2 groups. Group 1 (n = 258) includes diabetic patients without foot lesions and group 2 (n = 163) includes patients suffering from a diabetic foot ulcer. The HRQoL of the sample was assessed by using the SF-36 Health Questionnaire. The overall HRQoL score was 68.58 ± 18.24 in group 1 and 50.99 ± 18.98 in group 2 (P < .001). The diabetic foot-related etiological factors that significantly reduce these patients' HRQoL are neuropathy, amputation history, and poor metabolic control (P < .001). Quality of life was lower in women with diabetic foot than in men. Neuropathy--regarded as the main etiological factor in the diabetic foot--also proved to be a variable that reduces the HRQoL. Paradoxically, peripheral vascular disease did not prove to have a negative impact on the quality of life.