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Background: National Institutes of Health Stroke Scale (NIHSS) is the most validated clinical scale for stroke recognition, severity grading, and symptom monitoring in acute care and hospital settings. Numerous modified prehospital stroke scales exist, but these scales contain less clinical information and lack compatibility with in-hospital stroke scales. In this real-life study, we aimed to investigate if NIHSS conducted by paramedics in the field is a feasible and accurate prehospital diagnostic tool. Methods: This prospective cohort study is part of Treat-NASPP (Treat-Norwegian Acute Stroke Prehospital Project) conducted at a single medical center in Østfold, Norway. Sixty-three paramedics were trained and certified in NIHSS, and the prehospital NIHSS scores were compared with the scores obtained by in-hospital stroke physicians. Interrater agreement was assessed using a Bland-Altman plot with 95% limits of agreement. In secondary analysis, Cohen κ was used for the clinical categories NIHSS score of 0 to 5 and ≥6. As a safety measure, prehospital time was compared between paramedics conducting NIHSS and conventional paramedics. Results: We included 274 patients. The mean difference in NIHSS scores between the paramedics and the stroke physicians was 0.92 with limits of agreement from −5.74 to 7.59. Interrater agreement for the 2 clinical categories was moderate with a κ of 0.58. The prehospital NIHSS scoring was performed mean (SD) 42 (14) minutes earlier than the in-hospital scoring. Prehospital time was not significantly increased in the NIHSS-trained paramedic group compared with conventional paramedics (median [interquartile range] on-scene-time 18 [13–25] minutes versus 16 [11–23] minutes, P =0.064 and onset-to-hospital time 86 [65–128] minutes versus 84 [56–140] minutes, P =0.535). Conclusions: Paramedics can use NIHSS as an accurate and time efficient prehospital stroke severity quantification tool. Introducing NIHSS in the emergency medical services will enable prehospital evaluation of stroke progression and provide a common language for stroke assessment between paramedics and stroke physicians. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03158259.