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Two control groups were used: control group 1, with known risk factors including diabetes mellitus, and control group 2, with all risk factors without diabetes mellitus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Outcome Measures<\/jats:title><jats:p>Statistical associations between amputee and control group FRS scores, CACS, and other cardiac risk factors were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The study included 57 nontraumatic and 19 traumatic amputees with an average age of 62.4 years. Sixty\u2010six amputees were in the low\u2010to\u2010intermediate cardiac risk groups according to FRS. Despite this classification, the mean CACS were significantly higher in amputees (1285 \u00b1 18) than in either of the control groups: control group 1 (540 \u00b1 84) and control group 2 (481 \u00b1 11), <jats:italic>P<\/jats:italic> &lt; .001. CACS also were significantly higher in the nontraumatic subject group (1595 \u00b1 12) compared with the traumatic group (356 \u00b1 57; <jats:italic>P<\/jats:italic> &lt; .001). Upon categorization of CACS based on probability of coronary artery disease (CAD), 76% of amputees had a CACS &gt;100 and 38% of amputees had a CACS &gt;1000. Interestingly, CACS were almost the same in finger\/toe amputations compared with an above\u2010knee amputation, indicating an already ongoing CAD process irrespective of level of amputation. The predominant clinical significant cardiac risk factors in amputees are hypertension (89.5%), <jats:italic>P<\/jats:italic> &lt; .005; chronic kidney disease (31.6%), <jats:italic>P<\/jats:italic> &lt; .001; dyslipidemia (72.4%), <jats:italic>P<\/jats:italic> &lt; .04; and insulin resistance. Total cholesterol, low\u2010density lipoprotein, and high\u2010density lipoprotein levels were nonsignificantly low in all amputees. Triglycerides were particularly higher in traumatic patients compared with nontraumatic patients, with the triglycerides\/high\u2010density lipoprotein ratio &gt;7.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study demonstrates that amputees have a much greater burden of underlying atherosclerotic disease as detected by CACS than do control subjects matched by Framingham risk stratification. 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