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Objective: To study the effect of folate treatment on homocysteine (HCY) levels in patients with Coronary Artery Disease (CAD). We also made an attempt to analyze HCY levels in relation to other risk factors present in these patients. Materials and Methods: The study was a randomised, non-blind clinical trial carried out in 84 angiographically documented CAD patients and 40 controls (angiographically proved normal or treadmill test negative). Biochemical analyses of glucose, insulin, HCY, lipid profile and C-Reactive Proteins (CRP) were conducted in serum samples collected from these patients. Treatment with folic acid (5 mg/day) for 3 months was given to patients with hyperhomocysteinemia and the post- treatment HCY levels were analyzed. Results: The mean plasma HCY level in control volunteers was found to be 17.85±1.4 μmol/L, which was significantly lower than those in CAD patients (24.69±2.8 μmol/L). The levels were higher in non-diabetic patients (30.33±3.9 μmol/L) as compared to non-diabetic controls (18.18±1.6 μmol/L) as well as diabetic patients (14.53±1.43 μmol/L), irrespective of the presence of hypertension. No correlation was found between total HCY (t-HCY) levels and serum glucose, insulin, triglycerides, VLDL, LDL, HDL, cholesterol or CRP levels. A negative correlation was found between t-HCY levels and the age of the patients. The HCY levels were highest in the younger age group of patients (30-40 years) (49±7.8 μmol/L). There was a significant reduction in t-HCY levels after the folate treatment in mild and moderate hyperhomocystienemic patients but the reduction in patients with severe hyperhomocysteinemia was not significant. Conclusion: CAD patients have higher HCY levels than subjects without CAD. Indian diabetic patients have lower levels of t-HCY irrespective of the presence of cardiac disease. Folate treatment decreases the t-HCY levels in homocysteinemia and thus can be used in treatment of homocysteinemia. [ABSTRACT FROM AUTHOR]