With the advance of endovascular retrieval device for the cerebral thrombosis, it enables us to obtain a fresh thrombus of cerebral occlusion-site even in stroke survivors. We investigated the histological composition of retrieved thrombus and different effect of intravenous thrombolysis (IVT) according to the histological compositions of clots. We reviewed clinical, radiological, and interventional data of acute ischemic stroke patients from prospectively collected stroke and neurointervention registry at a stroke referral center from July 2014 to Jan 2016. The response to IVT was assessed by the change of clot burden score from initial CT angiography to digital subtraction angiography. The proportion of red blood cells (RBC), congregated fibrin/platelet, and white blood cells of the thrombus was analyzed by semi-automated color-based segmentation method (Positive Pixel Count Algorithm, Aperio scanscope). Patients were classified into RBC-dominant and fibrin-dominant or mixed group using receiver operating characteristic (ROC) curve analysis. Sixty patients were enrolled including 33 thrombus-available and 27 thrombus-unavailable patients. Thrombus-available group more likely to have cardioembolism and vessel sign, worse clot burden score, and use of retrieval stent. All 60 patients who received IVT, 35 patients showed IVT response and 25 patients did not show. The IVT-responsive group had more severe stroke (baseline NIHSS; 16.8±4.0 vs. 13.8±5.1, p=0.012), and showed more RBC-dominance (50.0% vs. 5.9%, p=0.007). Multivariate logistic regression analysis model revealed RBC dominance was an only variable influencing the good response to IVT (OR 15.816; 95% confidence interval 1.368-182.897, p=0.027). In analysis of characteristics according RBC ratio, the vessel signs and symptomatic hemorrhage according to the RBC ratio was more prevalent in patients with higher tertile than in those with lower levels. This study shows the histological composition of thrombus might lead to the different clinical characteristics, especially the response to IVT. The RBC dominance can be an important factor affecting the response to IVT, comparable with clinical or radiological findings in this study. The response to IVT appears to be influenced by histopathological features of retrieved thrombi and further studies are need to evaluate clinical implication.