Key PointsQuestionIs application of high-definition cathodal transcranial direct current stimulation (HD C-tDCS) as a noninvasive targeted acute ischemic stroke treatment strategy feasible and well-tolerated, and does it show signals of beneficial effects?FindingsIn this randomized clinical trial enrolling 10 patients (7 active, 3 sham), HD C-tDCS was started within a median 12.5 minutes of randomization in final enrolled patients and showed good tolerability with signals of favorable effects on salvage of threatened tissue.MeaningThese results suggest that HD C-tDCS is a noninvasive targeted acute ischemic stroke treatment strategy that can be efficiently applied in emergency settings and warrants testing in larger multicenter trials.