PURPOSE: The purpose of this study was to analyze the influence of a diabetic foot ulcer on all-cause and cardiovascular disease (CVD) mortality. DESIGN: Retrospective case-control study. SUBJECTS AND SETTING OUTPATIENTS: Eighty-eight patients with new-onset diabetic foot ulceration (DFU) were paired with 176 patients without DFU (controls). The study setting was the Department of Endocrinology, Sun Yat-sen Memorial Hospital, located in Guangzhou, China. METHODS: Cause-specific mortality was recorded during a median follow-up duration of 6.20 years up to 1 March 2016. Records review dates were from January 1, 2004, to December 31, 2010. RESULTS: The all-cause mortality rate for the DFU group and the control group was 48.9% and 22.7%, respectively. The risk of all-cause death in the DFU group was 3.126 times higher than that in the control group (risk ratio [RR]= 3.126; 95% CI, 1.998-4.891; P = .000). The CVD mortality rate of the DFU group and the control group was 12.5% and 6.8%, respectively. The risk of CVD death in the DFU group was 3.277 times higher than that in the control group (RR = 3.277; 95% CI, 1.392-7.715; P = .007). CONCLUSIONS: Development of a diabetic foot ulcer was associated with a significantly higher all-cause and CVD-related death risk than that in a control group of persons with diabetes mellitus without DFU.