Background and Purpose- We aimed to characterize acute ischemic stroke patients who have an immeasurable deficit on the admission National Institutes of Health Stroke Scale (NIHSS), and to evaluate their long-term outcome. Methods- We retrospectively compared all acute ischemic stroke patients with an admission NIHSS of 0 in the Acute Stroke Registry and Analysis of Lausanne from 2003 to 2013 with all other acute ischemic stroke patients. We compared demographics, clinical, radiological, and laboratory findings. Outcome was considered favorable at 3 months if the modified Rankin Scale score corrected for prestroke disability was ≤1. Stroke recurrences >12 months were also assessed. Results- Comparing 108 NIHSS zero (NIHSS=0) patients with the 2889 other strokes by multivariate analysis, NIHSS=0 had lower prestroke disability, longer onset-to-hospital delays and more lacunar and infratentorial strokes. NIHSS=0 patients were less likely to have early ischemic changes on acute computed tomography, had less arterial pathology and lower creatinine levels. They were more likely to have favorable modified Rankin Scale score after correction for prestroke modified Rankin Scale score (zero versus others: 83.2% versus 44.6%) and less likely to die (3.9% versus 13.3%) at 12 months. Stroke and transient ischemic attack recurrence rates were similar (11% versus 11.4%), however. Conclusions- Patients with NIHSS=0 strokes are characterized by lacunar and infrantentorial strokes, normal acute computed tomography, and less arterial pathology. However, a significant proportion face recurrent ischemic events and persistent handicap at 12 months. Therefore, NIHSS=0 stroke patients require aggressive secondary prevention and adequate follow-up.