This study describes the impact of diabetic foot ulcers (DFUs) on health-related quality of life (HRQoL) using a generic instrument including 8 domains. Data were obtained from 54 patients with DFU who were compared with 78 patients who had diabetes without foot ulcer. HRQoL was measured using the Iranian version of Medical Outcome Study–Short Form (SF-36). The fasting plasma glucose, creatinine, glycosylated hemoglobin (HbA1c), and urine microalbumin as well as ankle-brachial pressure index (ABI) were measured for all participants in the 2 groups. In all, 51.9% of patients with DFU had ABI scores of <0.9 compared with only 11.8% of the control group (P < .001). No differences were found in any of the treatment characteristics (oral/insulin therapy) between the 2 groups (case/control). HRQoL evaluated by the SF-36 questionnaire, in particular in the areas of physical function, is lower in patients with diabetes with foot ulcers compared with patients with diabetes without foot ulcers (41.04 ± 22.69 vs 56.67 ± 25.57; P < .01). After adjusting by sex, 2 domains of physical functioning and bodily pain as well as the total HRQoL score in patients with DFU were lower than in patients with diabetes (P < .001). This study showed that physical functioning and bodily pain along with total score of HRQoL were important aspects that were lower in patients with DFU than in patients with diabetes. Gender was considered as a confounding factor, which was omitted in multivariate analysis.