Background and purpose Successful reperfusion can be achieved in more than two-thirds of patients with usual large-vessel occlusion stroke causes treated with mechanical thrombectomy. However, the safety and outcomes after mechanical thrombectomy in the setting of large-vessel occlusion related to infective endocarditis is not known. In this study, we investigated the impact of mechanical thrombectomy in infective endocarditis patients on angiographic and clinical outcomes. Methods This was a multicenter study from five comprehensive stroke centers. We compared the outcomes of mechanical thrombectomy treated stroke patients due to infective endocarditis with patients presenting atrial fibrillation. Clinical outcomes included 90-day modified Rankin Scale, symptomatic intracerebral hemorrhage, and mortality. Results Between June 2013 and March 2019, 28 patients presenting large-vessel occlusion stroke due to IE were included. These cases were matched with 84 large-vessel occlusion stroke related to atrial fibrillation. Successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b/3) was obtained in 85.7%. Symptomatic intracranial hemorrhage, favorable outcome and mortality rates were respectively 8.0%, 25.9%, and 25.9%. In the case–control analysis, we demonstrated no difference in terms of successful reperfusion, procedural complication, symptomatic intracranial hemorrhage, and mortality rates. Three-month favorable outcome was less often achieved in the infective endocarditis group. Conclusions Mechanical thrombectomy of infective endocarditis patients presents similar safety and angiographic results compared to patients suffering from atrial fibrillation.