<i>Aim of the Study:</i> Previous studies have suggested that total plasma homocysteine (HCY) is an important cardiovascular risk factor because of its interaction with vascular smooth muscle cells, endothelium function, plasma lipoprotein, coagulation factors and platelets. The aim of this study was to evaluate a possible relationship between HCY levels and the severity of coronary artery disease (CAD) and its prognostic value in patients with unstable angina (UA). <i>Methods and Results:</i> Ninety-four patients with UA were recruited and underwent coronary angiography and in some cases myocardial revascularization. The primary end point was the severity of CAD. The clinical end points were the recurrence of UA and the compositive end point of the occurrence of cardiac death and re-hospitalization due to acute coronary syndrome. HCY levels were shown to be poorly correlated with the severity of CAD. After 48 months’ of follow-up, a graded relationship between HCY levels and recurrence of UA and compositive end point was found (p < 0.001). <i>Conclusions:</i> In the light of events occurring during the follow-up period, it was concluded that total plasma HCY is a strong predictor of recurrence of UA.