The outcomes of endovascular therapy (EVT) across sexes for large infarcts remain unclear. This study aimed to evaluate the impact of sex on the outcomes of EVT or medical management for patients with large infarcts.In this secondary analysis of the ANGEL-ASPECT (Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core) randomized controlled trial conducted at 46 stroke centers across China between October 2, 2020, and May 18, 2022, we compared baseline characteristics and clinical outcomes between males and females, and each cohort further divided into EVT and medical management groups. The primary outcome was the 90-day modified Rankin Scale score distribution. Safety outcomes included symptomatic intracranial hemorrhage within 48 hours and mortality within 90 days.There were 176 of 455 patients enrolled in the ANGEL-ASPECT trial who were female. There were 54.0% (95/176) of females and 48.4% (135/279) of males who underwent EVT. The treatment effect of EVT did not vary in both sexes with large infarcts (all P>0.05 for interaction). Compared with medical management, EVT improved 90-day functional outcomes for both males (3 [2-5] versus 4 [3-5]; common odds ratio, 1.94 [95% CI, 1.27-2.97]; P=0.002) and females (4 [3-6] versus 5 [4-6]; common odds ratio, 2.50 [95% CI, 1.41-4.45]; P=0.002). The symptomatic intracranial hemorrhage rate was not different in both treatment groups across both sexes (males, 5.2% versus 2.8%; odds ratio, 2.05 [95% CI, 0.56-7.50]; P=0.278; females, 7.4% versus 2.5%; odds ratio, 2.89 [95% CI, 0.55-15.14]; P=0.210).In patients with large ischemic core, the treatment effect of EVT did not differ between females and males, with better outcomes with EVT versus medical management, without an increased risk of symptomatic intracranial hemorrhage. These findings emphasize the need for equal attention and care for both sexes with large infarcts in clinical practice.URL: https://www.clinicaltrials.gov; Unique identifier: NCT04551664.