This study aimed to investigate regional levels of TAT (thrombin-antithrombin complex), PIC (plasmin-α2 plasmin inhibitor complex), t-PAIC (tissue plasminogen activator-plasminogen activator inhibitor complex), sTM (soluble thrombomodulin), and D-dimer, along with their associations with clinical and procedural characteristics in patients with acute ischemic stroke undergoing endovascular thrombectomy.We retrospectively analyzed 166 consecutive patients with acute ischemic stroke (62±11.54 years of age, 34.3% women) using prospectively maintained clinical databases and blood samples from local ischemic (proximal to thrombus) and systemic (femoral artery, self-control) arterial compartments. Levels of TAT, PIC, t-PAIC, and D-dimer were significantly elevated, whereas sTM was significantly reduced, in local ischemic regions compared with their systemic levels. Each 1-unit increase in ischemic TAT (adjusted odds ratio [aOR], 1.086 [95% CI, 1.03-1.145]; P=0.002; area under the curve [AUC], 0.833) and PIC (aOR, 1.337 [95% CI, 1.087-1.644]; P=0.006; AUC, 0.771) correlated significantly with higher symptomatic intracranial hemorrhage risk. Additionally, each 1-unit increase in ischemic TAT (aOR, 1.076 [95% CI, 1.016-1.139]; P=0.013; AUC, 0.797), PIC (aOR, 1.554 [95% CI, 1.194-2.022]; P=0.001; AUC, 0.798), and sTM (aOR, 0.769 [95% CI, 0.615-0.961]; P=0.021; AUC, 0.756) was significantly associated with an increased risk of an unfavorable 90-day outcome (modified Rankin scale of 3-6). These hemostatic molecules, individually or combined, significantly improved the predictive power of conventional risk factors, as evidenced by significant increases in net reclassification improvement and integrated discrimination improvement (all P<0.01).We observed a hyperactive state of the coagulation-fibrinolysis system within the local ischemic region during hyperacute stroke. Rapid automated measurement of hemostatic molecular markers, particularly TAT, PIC, and sTM, during intra-arterial procedures may provide additional information for stroke risk stratification and therapeutic decision-making, and warrants further investigation.