Background Simultaneous multivessel occlusions (MVOs) are a rare condition, which may be encountered during endovascular thrombectomy (EVT) for acute ischemic stroke. This study aimed to investigate the prevalence, associated factors, and outcome of patients with acute ischemic stroke and MVO who underwent EVT. Methods Consecutive patients with acute ischemic stroke who received EVT between September 2014 and April 2021 were included. Acute MVO was defined as simultaneous occlusions of ≥2 intracranial or extracranial major vessels in either bilateral anterior circulation or anterior plus posterior circulation. Patients’ baseline characteristics and outcome of MVO were analyzed. Results Of 602 patients with acute ischemic stroke (mean age, 71±13 years; male, 53.1%) who received EVT, 11 patients (1.8%) had acute MVO. The involved vessels included bilateral internal carotid arteries in 3, bilateral middle cerebral arteries in 4, vertebral artery and distal middle cerebral artery in 1, and internal carotid artery and distal posterior cerebral artery in 3 patients. Preadmission dependence (modified Rankin scale score >2), higher initial stroke severity, and posterior cerebral artery occlusion were more frequently found in MVO. The cause of MVO included large vessel atherosclerosis in 4, cardioembolic in 4, cancer‐related hypercoagulability in 2, and postpartum in 1 patient. Several patients had received simultaneous multitargeted EVT, but only 4 of them achieved optimal reperfusion in both vessels. Compared with patients without MVO, those with MVO had higher mortality (adjusted odds ratio, 6.75; 95% CI, 1.93–23.6) and poor functional outcome (common odds ratio for 1‐point improvement at modified Rankin scale, 0.14, 95% CI, 0.05–0.45) at 90 days. Conclusion Acute simultaneous MVO in patients who underwent EVT is a rare yet devastating condition. Multitarget mechanical thrombectomy to achieve reperfusion is challenging but still possible.