Objective To investigate the changes in platelet parameters and their relationship with malignant brain edema (MBE) in patients with acute cerebral infarction after edaravone and dexborneol trometamol combined with thrombolytic therapy.Methods A total of 167 patients with ACI who visited our hospital from December 2022 to September 2024 were included. They were divided into the MBE group (n=46) and the non-MBE group (n=121) based on whether MBE occurred. Repeated measures analysis of variance was used to analyze platelet parameters and hemorheological indicators. Multivariate linear regression was used to analyze the correlation between platelet parameters and hemorheological indicators. COX regression was used to analyze the correlation between platelet parameters and MBE. With MBE as the outcome variable, a ROC curve was established and the area under the curve (AUC) was calculated. The restricted cubic spline method was used to analyze the dose-response relationship of platelet parameters to MBE. Results After treatment,the platelet volume (MPV), platelet distribution width (PDW), platelet aggregation rate (PAgT), platelet adhesion rate (PAdT), plasma viscosity, whole blood high shear viscosity, whole blood low shear viscosity, hematocrit, and erythrocyte aggregation index of the two groups were lower than those before treatment, while the platelet count (PLT) and platelet distribution (PCT) were higher than those before treatment (all P<0.05). The MPV, PDW, PAgT, and PAdT, plasma viscosity, whole blood high shear viscosity, whole blood low shear viscosity, hematocrit, and erythrocyte aggregation index of the MBE group at 7 and 14 days after treatment were higher than those of the non-MBE group, while PLT and PCT were lower than those of the non-MBE group. The differences between the groups were statistically significant (all P<0.05). The results of repeated measures variance analysis showed that the influence of the time factor on platelet parameters and hemorheological indicators varied depending on whether MBE occurred after treatment. The results of multiple linear regression analysis showed that platelet parameters MPV, PDW, PAgT, and PAdT were significantly positively correlated with hemorheological indicators, while PLT and PCT were significantly negatively correlated with hemorheological indicators (all P<0.05). The results of COX regression analysis showed that after adjusting for multiple confounding factors, high levels of MPV, PDW, PAgT, and PAdT had a higher risk of MBE than low levels of PLT and PCT (all P<0.05). The results of ROC curve analysis showed that the AUC of platelet parameters combined for predicting the risk of MBE was 0.848 (95% CI:0.829~0.914), with a sensitivity of 76.8% and a specificity of 83.6%. The results of restricted cubic spline model analysis showed that MPV, PDW, PAgT, and PAdT were significantly positively correlated with MBE, while PLT and PCT were significantly negatively correlated with MBE.Conclusion After ACI patients received edaravone ketocarbonate combined with thrombolytic therapy, the changes in platelet parameters were significantly correlated with hemorheological indicators and the occurrence of MBE. Moreover, there was an interaction between platelet parameters and hemorheological indicators on the occurrence of MBE. The range of platelet parameters is helpful for predicting the risk of MBE and providing guidance for clinical intervention