Homocysteine (tHcy), a sulfur-containing amino acid, is produced during the metabolism of the essential amino acid methionine. In this metabolic pathway, methionine is demethylated to yield adenosine and homocysteine. Which may then enter a two-step pathway to become irreversibly transsulfurated to cysteine in a reaction requiring the vitamin B6-dependent enzyme cystathionine β-synthase. Alternatively, it may be remethylated back to methionine utilizing folate and vitamin B12. Increased plasma levels of tHcy (due to genetic or acquired factors) are associated with atherogenic and thrombotic tendencies, at least in part, by depressing endothelial function, (possibly through nitric oxide-dependent mechanisms) are promote thromboemblic disease by causing oxidative injury to the endothelium, altering the coagulant properties of the blood, and impairing endothelium-dependent vasomotor regulation. The aim of the present work is to assess the plasma levels of homocysteine, vitamin B12 and folate in patients (pts) with peripheral arterial disease in relation to associated risk factors (Diabetes, Smoking, and Hyperlipidemia). In conclusion, Homocysteinemia -an intermediate metabolite in methionine metabolism- apparently plays an important role in the pathphysiology of peripheral arterial disease, particularly in synergism with associated risk factors, with significantly higher level of tHcy and significantly lower levels of Folate and Vitamin B12 in the patients with peripheral vascular diseases compared to controls. Smoking, diabetes and hypercholestermia not only enhance the atherogeneic and peripheral vascular effects of homocysteine, but surprisingly increase their plasma levels with no clear explanation. Dietary supplementation with Folate and Vitamin B12 are recommended in pts with peripheral arterial disease to mitigate the adverse effects of Homocysteine.