Hybrid assistive neuromuscular dynamic stimulation (HANDS) is a therapeutic approach to facilitate the use of the paretic upper extremity in daily living by combining assistive neuromuscular electrical stimulation with a wrist-hand splint for patients with moderate to severe hemiparesis. Usually in HANDS therapy, patients use these devices eight hours a day and perform intensive hand rehabilitation for three weeks.We examined the change of short intracortical inhibition (SICI) and reciprocal inhibition (RI) to examine the effects of the HANDS therapy to the cortico-spinal systems in chronic stroke patients.In many patients, the SICI in an affected hemisphere was decreased, and RI of a paretic arm was increased after HANDS therapy. It means the excitability of an affected cortex was increased and reciprocal inhibition of a paretic arm was enhanced in spinal level. These changes were correlated with improvement of motor function after treatment. Furthermore, in HANDS therapy, the change of neurophysiological factor and motor function was seen in stroke patients with chronic phase more than a few years from the onset of stroke.HANDS therapy might be considered a useful choice as a therapeutic approach to paretic hand of chronic stroke patients.