Objective: Elevated homocysteine levels induce a hypercoagulable state and make the clot more resistant to fibrinolysis. In this prospective observational study, we investigated the influence of homocysteine levels on infarct-related artery (IRA) patency and flow as determined with regard to thrombolysis in myocardial infraction (TIMI) flow grade and corrected TIMI frame count (CTFC). Materials and Methods: Sixty-one patients who received fibrinolytic therapy for a first ST elevation myocardial infarction (STEMI) within 12 hours of chest pain were included. Coronary angiography was performed according to the Judkins technique within 72 hours after fibrinolytic therapy. Total plasma homocysteine level was determined by the high-performance liquid chromatography method with fluorescence detection. Statistical analysis was performed using Chi-square, Student’s t and Pearson correlation tests. Logistic regression analysis was used to determine the predictors of IRA occlusion. Results: Of the 61 patients, 22 (36.1%) had an occluded IRA (group 1), 39 (63.9%) had a patent IRA (group 2). Mean plasma homocysteine levels were found to be significantly higher in the group 1 compared to the group 2 (18.5±9.6 µmol/L vs 14.3±5 µmol/L, p=0.04). In addition, we found a significant positive correlation between CTFC and plasma homocysteine levels (r=0.415; p<0.01). In multiple logistic regression analysis, high levels of plasma homocysteine (OR=1.2; 95% CI 1.1-1.25; p=0.03) and being a non-smoker (OR=5.9; 95% CI 1.1-31.6; p=0.03) were found to be significant independent predictors of having an occluded IRA. Conclusion: There is an inverse relation between plasma homocysteine levels and IRA patency and flow in patients receiving fibrinolytic therapy for STEMI.