Smoking and diabetes are risk factors for coronary artery disease which increase homocysteine level. In this study, the role of homocysteine in patients with acute coronary syndrome with a history of cigarette smoking and risk of diabetes was examined. One-hundred ninety three (193) patients with acute coronary syndrome (unstable angina, STEMI and non-STEMI) referred to the Heart Center of Imam Ali (AS) Hospital in Kermanshah were studied. Diabetic patients who were active smokers were selected as study group. Non-diabetic patients who had no history of smoking or at least six months passed since they left smoking were considered as controls. Blood samples were taken during fasting and then homocysteine levels were measured by ELISA method. The mean serum homocysteine level in patients who were only smokers was 19.5-11.4 mg/dl. This was 19.2-9.2 mg/dl in patients who only had diabetes. The homocysteine level in patients who were still smoking and also had diabetes was 17-9.6 mg/dl. This was 19.1-2.10 mg/dl in patients who did not use cigarette and did not have diabetes. The statistical analysis did not show any significant differences between different categories of patients (p: 0.609). The results of the present study showed that although the homocysteine level has increased in patients with acute coronary syndrome, diabetes or smoking does not influence the elevated levels of homocysteine in patients with acute coronary syndrome.