Donepezil has been proven effective in the treatment of Alzheimer's disease and vascular dementia. However, its effects on the cognitive neural network have not been fully investigated. The purpose of this study was to evaluate the effect of donepezil on reorganisation of the cognitive neural network in patients with post-stroke cognitive impairment using functional MRI (fMRI). Fourteen patients with stroke in the right hemisphere were enrolled. Participants were randomly assigned to the experimental or the control group. Donepezil (5 mg) or placebo was administered daily for four weeks. Cognitive function assessment was performed before and immediately after treatment, and repeated one month after cessation of treatment. fMRI was performed before and after treatment. Ten out of 14 patients (six in the experimental group, four in the control group) successfully completed all experimental processes. The experimental group showed significant improvements in the Mini-Mental Status Examination during the post-treatment evaluation and one-month follow-up compared to the pre-treatment evaluation (p < .05). No improvement was observed in the control group. In the experimental group fMRI showed increased activation in both prefrontal areas, both inferior frontal lobes, and in the left inferior parietal lobe. Increased recruitment of the parieto-frontal networks in the selected patients was considered to be a neural correlate of cognitive improvement induced by donepezil.