Peripheral arterial occlusive disease (PAOD) affects 12% of the general population and 20% of persons older than 70 years. The most important causes of PAOD are: atherosclerosis and arteritis. Atherosclerosis remains the leading cause of death and disability worldwide. Considerable evidence has established elevated plasma homocysteine as an important risk factor for atherosclerotic disease. The association between hyperhomocysteinemia and arteritis (the 2nd most common cause of PAOD) has been discussed by some studies, too. Hyperhomocysteinemia is a metabolic disorder that is mainly due to deficiencies of folate, vitamin B12 and vitamin B6, or genetic defects of homocysteine metabolism. Most patients with elevated homocysteine levels can be easily treated by supplementation with B vitamins. In fact, folic acid was recently approved as a supplement in cereal grain products. Levels of folic acid achieved by this means are sufficient to significantly reduce plasma homocysteine levels, an effect that may have therapeutic efficacy. Factor V Leiden is a relatively newly described syndrome of thrombophilia. It is the most common cause of thrombosis, although it alone is a relatively low risk factor for thrombosis. Some studies suggested that the prevalence of this syndrome might be increased in patients with PAOD. However, a meta-analysis of 33 studies found no significant association. This study measured Hcy level in 43 patients with PAOD and 20 control subjects in order to estimate the prevalence of hyperhomo-cysteinemia in both groups. The patients were divided into two groups: atherosclerosis (23 patients) and arteritis (20 patients). FVL was also investigated in all subjects of this study to assess its role in arterial disease. The results of the study showed higher mean level of Hcy in patients with PAOD (14.5 μmol/L) compared to controls (8.8 μmol/L). Hyperhomocysteinemic subjects constituted 41.9% of patients and only 5% of controls. Comparison between the two groups of patients: atherosclerosis and arteritis, revealed no significant difference. Only 3 of the patients had factor V Leiden and none of the controls. The 3 patients had normal Hcy level. It is concluded from this study that there is a definite association between Hcy level and PAOD in Egyptian patients. However, this doesn’t prove the causal role of Hcy in PAOD, as it may be an effect of cardiovascular disease and not the cause. It is also unclear whether supplementation with folic acid will reduce risks of cardiovascular disease. Currently, more than 20 prospective, worldwide, interventional trials involving at least 100,000 participants are examining whether lowering plasma homocysteine levels with supplemental B vitamins will prevent mortality and morbidity from PAOD. We recommend that a similar prospective, large scale, randomized interventional trial should be started in Egypt, and the results should join the worldwide trials. In the time being, vitamin B supplementation should be started for every patient with PAOD in Egypt, as it is inexpensive and safe.