We investigated the relationship between serum cystatin C levels and the prognosis of diabetic foot ulcerations (DFU). A population-based cohort study involving 1018 patients with type 2 diabetes was conducted. These patients recruited and divided into two groups: nondiabetic foot ulcer group (NDF, n=865, 85.5%) and diabetic foot ulcer group (DFU, n=147, 14.5%).After a 1-year-follow-up, DFUs were grouped into healing (n=110, 74.8%) and nonhealing (n=37, 25.2%) group based on the clinical prognosis. Compared with the healing group, the nonhealing group were older, had long diabetic duration and had significantly increased serum cystatin C concentrations in DFU (p<0.01). After adjustments for age, diabetes duration, renal function and infection control, multiple logistical regression analysis revealed that cystatin C remained associated increased risk of undesirable DFU outcome (OR=7.279, 95% CI: 1.299–40.784, p<0.05). When divided into quartiles according to cystatin C levels, the healing rate of Quartile 4 was significantly lower (57.9%) compared with other groups (p<0.01). The odd is ratio (OR) analysis showed that the risk of undesirable DFU outcome in Quartile 4 was significantly higher (OR=4.554, 95% CI: 3.14–5.12, p<0.05) compared with that in Quartile 1. We concluded that there was a strong and independent association between serum cystatin C and diabetic foot ulceration prognosis, cystatin C>1.35 mg/L predicts more than sixfold increased risk of incurable foot ulceration.