OBJECTIVE This study aims to compare the levels of osteoprotegerin (OPG) and 25-hydroxy vitamin D (25(OH)D) in patients with diabetic foot and patients with newly diagnosed type 2 diabetes mellitus (DM) and to investigate the prevalence and severity of 25(OH)D insufficiency in patients with diabetic foot. METHODS This prospective study was conducted on 105 patients including 58 patients with diabetic foot (42 males, 16 females; mean age 63.6 years; range, 31 to 90 years), who applied to our hospital between June 2014 and May 2015, and 47 newly diagnosed type 2 DM patients (27 males, 20 females; mean age 51.4 years; range, 29 to 85 years) (control group). 25(OH)D and osteoprotegerin serum levels in both groups were measured and compared. RESULTS Osteoprotegerin levels in diabetic foot group were significantly higher than the control group (p<0.05). The 25(OH)D levels in diabetic foot group were significantly lower than the control group (p<0.05). There were positive correlations between OPG levels and C-reactive protein (CRP) and creatinine levels in patients with diabetic foot. CONCLUSIONS Elevated levels of OPG in patients with diabetic foot may display the severity of the clinical status due to its positive correlation with CRP and creatinine. We detected severe 25(OH)D deficiency in the majority of diabetic foot patients. Vitamin D supplementation may be required in diabetic foot patients to prevent unfavorable immunologic alterations.