The underlying structure of National Institutes of Health Stroke Scale (NIHSS) as the most widely used scale in clinical trials has been the focus of little attention. The aim of the current study was to elucidate the clustering pattern of NIHSS items in ischemic stroke patients. A series of 152 consecutive patients with first-ever ischemic strokes admitted to a university affiliated hospital were enrolled. NIHSS score was estimated on admission and correlation coefficients between its items were calculated. Further, exploratory factor analysis was used to study the clustering pattern of NIHSS items. Extinction neglect, visual field, and facial palsy were weakly associated with other NIHSS items. Factor analysis led to a four-factor structure. Factors 1 and 3 were determined by left brain function as items of right arm and leg motor, language and dysarthria loaded on both of them. By contrast, factor 2 reflected right brain involvement. Since visual field and ataxia loaded on factor 4, this factor was primarily associated with posterior strokes. Our study shows that a four-factor structure model is plausible for NIHSS. Further, for the first time, a single distinct factor is identified for posterior strokes.