BackgroundDespite the central origin of stroke affecting the primary motor cortex M1, most physical and occupational rehabilitation programs focus on peripheral treatments rather than addressing the central origin of the problem. This highlights the urgent need for effective protocols to improve neurological rehabilitation and achieve better long-term functional outcomes. ObjectivesOur hypothesis was that the bihemispheric delivery of transcranial direct current stimulation (tDCS) is superior to unihemispheric in enhancing motor function after stroke, in both the upper and lower extremities. Methods35 sub-acute ischemic stroke survivors were randomly divided into three groups: bihemispheric and unihemispheric treatment groups, or sham groups. Each participant received a 20-minute session of tDCS with an intensity of 2 mA during physical therapy sessions, three days a week, for four weeks. The outcomes were measured using Fugl-Meyer assessment scale, modified Ashworth scale, Berg balance scale, and serum brain-derived neurotrophic factor (BDNF) levels. ResultsOne-way ANOVA test indicated a significant effect of both treatment protocols on the upper extremity (p = < 0.001) and lower extremity (p = .034) for motor measures, but there was no difference between the two (p = .939). Kruskal Wallis test for spasticity showed a significant improvement in both treatment groups for elbow (p = .036) and wrist flexors (p = .025), compared to the sham group. However, there was no statistically significant difference in spasticity between uni- and bihemispheric stimulation for elbow (p = .731) or wrist flexors (p = .910). ConclusionThere is no statistically significant difference in efficacy between bihemispheric and unihemispheric tDCS in patients presenting with acute ischemic stroke. .