Background and Purpose- To date, no clinical score has become widely accepted as an eligible prehospital marker for large vessel occlusion (LVO) and the need of mechanical thrombectomy (MT) in ischemic stroke. On the basis of pathophysiological considerations, we propose that cortical symptoms such as aphasia and neglect are more sensitive indicators for LVO and MT than motor deficits. Methods- We, thus, retrospectively evaluated a consecutive cohort of 543 acute stroke patients including patients with ischemia in the posterior circulation, hemorrhagic stroke, transient ischemic attack, and stroke mimics to best represent the prehospital setting. Results- Cortical symptoms alone showed to be a reliable indicator for LVO (sensitivity: 0.91; specificity: 0.70) and MT (sensitivity: 0.90; specificity: 0.60) in acute stroke patients, whereas motor deficits showed a sensitivity of 0.85 for LVO (specificity: 0.53) and 0.87 for MT (specificity: 0.48). Conclusions- We propose that in the prehospital setting, the presence of cortical symptoms is a reliable indicator for LVO and its presence justifies transportation to an MT-capable center.