Evidence is accumulating that toll-like receptors (TLR) are involved in the initiation and progression of cardiovascular disease. Enhanced expression of these receptors on monocytes has been shown in patients with acute coronary syndrome (ACS). However, expression on platelets in this group of patients has not been evaluated yet. We aimed to demonstrate the possible relationship of platelet TLR-2 and TLR-4 expressions with stable coronary artery disease and ACS pathogenesis. In this observational case-control study, 40 patients diagnosed with ACS (unstable angina pectoris, non-ST-segment elevation and ST-segment elevation ACS), 40 patients diagnosed with stable coronary artery disease, and 40 age- and gender-matched subjects with normal coronary arteries were involved. Platelet TLR-2 and TLR-4 expressions were evaluated by flow cytometry in peripheral venous blood samples obtained before coronary angiography. A total of 120 patients (60.7 ± 12.3 years, 50% men) were included. Median platelet TLR-2 and TLR-4 expressions were greater in patients with ACS compared to those with stable angina pectoris and normal coronary arteries (29.5% vs 10.5% vs 3.0%, p <0.001 and 40.5% vs 11.5% vs 3.0%, p <0.001, respectively). Median platelet TLR-2 and TLR-4 expressions were also greater in patients with stable angina pectoris compared to those with normal coronary arteries (p <0.05). In conclusion, this is the first study demonstrating enhanced TLR-2 and TLR-4 expressions on platelets in patients with ACS. These findings may suggest that platelet TLR expression as a novel potential prophylactic and therapeutic target in ACS.