Background and Purpose—Patients with embolic large-vessel occlusion may present with additional coincidental acute occlusions within or distant from the involved territory, referred to as multivessel occlusion (MVO). Purpose of this study was to assess prevalence of MVO, associated factors, and clinical relevance in patients undergoing endovascular stroke treatment.Methods—Image data of consecutive endovascular candidates (n=720) with direct access to angiography were extracted from a prospective registry. Prevalence of MVO was assessed with multimodal magnetic resonance imaging/computed tomography and confirmed by intra-arterial angiography. Explorative analysis of associated factors and clinical relevance was evaluated using multivariable logistic regression including variables with P<0.15 in univariate comparison. Good functional outcome was defined as modified Rankin Scale score ≤2 at day 90.Results—MVO was present in 10.7% of patients (95% confidence interval [CI], 6.4%–13.0%). Two, 3, and 4 concomitant occlusions were found in 80.5%, 16.9%, and 2.6% of MVO cases, respectively. Detection rate on initial radiological report was 54.5%. Downstream MVO was present in around one third of MVO (n=27/77, 35.1%), whereas all other MVO (n=50/77, 64.9%) occurred in different territories. Independent factors related to MVO were statin treatment (adjusted odds ratio [aOR], 0.477; 95% CI, 0.276–0.827), higher systolic blood pressure (aOR per mm Hg increase, 1.014; 95% CI, 1.005–1.023), and primary occlusion site M2 (aOR, 1.870; 95% CI, 1.103–3.170). MVO was related to lower rates of successful reperfusion (aOR, 0.549; 95% CI, 0.316–0.953) and lower rates of good functional outcome (aOR, 0.437; 95% CI, 0.207–0.923).Conclusions—Every tenth patient subjected to angiography for endovascular stroke treatment experienced MVO in our series, and only half were prospectively identified on preinterventional diagnostic imaging. Patients with MVO had higher baseline systolic blood pressure and were less often medicated with statins, an observation that warrants external validation and evaluation regarding causality. Occurrence of MVO has implication for treatment decisions, negatively affects endovascular treatment success, and is predictive of worse clinical outcome.