Thrombus aspiration is useful in improving myocardial reperfusion in comparison to conventional percutaneous coronary intervention in patients with acute myocardial infarction. Nonetheless, assessment of thrombus aspiration efficacy is lacking. Aim of this study was to quantify by frequency domain optical coherence tomography (OCT) the amount of thrombus removal in patients with acute coronary syndromes undergoing manual thrombus aspiration, correlating it with the actual size of the retrieved material. Twenty-five consecutive patients with acute coronary syndrome were enrolled. OCT assessment of thrombotic lesions was performed before and after thrombus aspiration and repeated after stent deployment. OCT thrombus assessment was based on an established scoring technique. The aspirated material was analyzed by histology, and its planimetry was correlated with OCT-derived thrombus removal. The percentage of thrombus removal [(prethrombus aspiration minus post-thrombus aspiration)/(prethrombus aspiration × 100)] was 48.9; the delta measurement of the removed thrombus calculated by OCT correlated well with the planimetry-measured aspirated material (r = 0.56, P < 0.01). The present study showed the following: the thrombus score derived by OCT measurements correlated reasonably well with the planimetry measure of surface area of the actual aspirated material; after thrombus aspiration a large amount of residual thrombus can be appreciated at the target lesion site; and tissue components such as cholesterol debris and inflammatory cells can often be retrieved during thrombus aspiration.