BACKGROUND: The coagulation system is intrinsically linked to pathological mechanisms and progression of ischemic stroke. However, the role of preoperative coagulation function in determining the functional outcomes of acute ischemic stroke patients following large artery occlusion (AIS-LVO) has not been extensively evaluated in peer-reviewed literature. METHODS: We utilized logistic regression analyses, complemented by the construction of receiver operating characteristic (ROC) curves, to identify significant predictive factors for poor prognosis following endovascular thrombectomy (EVT). Additionally, subgroup analyses were conducted to further assess the prognostic efficacy of coagulation function across different subgroups. RESULTS: A total of 607 patients were enrolled, with 335 (55.19%) experiencing an unfavorable outcome. Multivariate regression analysis identified preoperative D-dimer and PTA as independent predictors of 3-month prognosis. After adjusting for confounders, elevated preoperative D-dimer levels (≥ 715 mg/L), identified by cut-off value, were a significant predictor of poor prognosis, with 2.51-fold higher risk compared to the normal range. Conversely, elevated PTA levels (≥ 85.5%) were significantly and inversely associated with poor prognosis, indicating a reduced risk of 0.39 times. Furthermore, the combination of elevated D-dimer and reduced PTA demonstrated a synergistic effect, markedly increasing the risk of poor outcomes in AIS-LVO patients. Subgroup analyses revealed that failed recanalization, comorbid diabetes, and non-middle cerebral artery (MCA) occlusion significantly influence the predictive value of D-dimer and PTA for clinical outcomes. CONCLUSION: Elevated admission D-dimer and reduced PTA levels are independent predictors of poor prognosis in patients with AIS-LVO, and there is a synergistic interaction between the two variables.