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Five-year mortality rates after new-onset diabetic ulceration have been reported between 43% and 55% and up to 74% for patients with lower-extremity amputation. These rates are higher than those for several types of cancer including prostate, breast, colon, and Hodgkin’s disease. These alarmingly high 5-year mortality rates should be addressed more aggressively by patients and providers alike. Cardiovascular diseases represent the major causal factor, and early preventive interventions to improve life expectancy in this most vulnerable patient cohort are essential. New-onset diabetic foot ulcers should be considered a marker for significantly increased mortality and should be aggressively managed locally, systemically, and psychologically. (J Am Podiatr Med Assoc 98(6): 489–493, 2008)