The aim of the study was to evaluate prevalence of hyperhomocysteinemia (HtHcy) in patients with acute coronary syndrome (ACS, incl. acute myocardial infarction and unstable angina) and in controls. We also estimated the role of homocysteine (Hcy) as a risk factor for new acute coronary events. Consecutive patients (N = 107) with ACS were recruited. Eleven patients were excluded from the study due to concomitant malignant tumors or renal insufficiency. The Hcy was 12.2±5.2 μmol/L in patients with ACS and 8.3±2.7 μmol/L in controls (p<0.0001). The HtHcy was defined as median value of Hcy (11.1μmol/L) in the ACS group. The Hcy values of patients with HtHcy had significantly higher values of creatinine, uric acid and triglycerides. Patients with recurrent ACS (new acute coronary event in a patient with a history of previous myocardial infarction) were not different from the Hcy values of patients with the first ACS. There was no relationship between Hcy and a new acute coronary event in patients with concomitant hypertension. Normotensive ACS patients with a recurrent acute coronary event had significantly higher values of Hcy than patients with the first ACS. We conclude that homocysteine has an impact on a new acute coronary event in normotensive patients. In hypertensive patients hyperhomocysteinemia seems to have no clear role in a new acute coronary event.