The pathophysiology of periodic leg movements in sleep (PLMS) is complex, and still lacks a consensus. Consecutive 35 patients with the diagnosis of acute supratentorial ischemic stroke and 35 age- and sex-matched control subjects were prospectively investigated. Clinical and sociodemographic evaluation and a whole-night polysomnographic recording were performed. In patients with supratentorial ischemic stroke, 27 patients (77.2%) had PLMS-index more than 5/h, and 19 out of 35 patients (54.3%) had PLMS-index more than 15/h; while only 10 participants (28.5%) in control group had PLMS-index more than 5/h, and 6 participants (17.1%) had PLMS- index more than 15/h (p < 0.05). None of the demographic variables showed statistically significant relationship with PLMS, such as gender (p = 0.952) and age (p = 0.435). Territorial localization of ischemic lesions showed no relation with the presence of PLMS (p = 0.867), PLMS- index (p = 0.432), or restless legs syndrome (p = 0.833). All patients demonstrated PLMS contralateral to ischemic lesion except eight patients with bilateral PLMS; these were also more prominent contralaterally. Our study supports the hypothesis that destructive lesions causing the loss of cortical or subcortical inhibition exerting on the reticular formation on spinal pathways could lead to the development of PLMS.